Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.

BACKGROUND: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. METHODS: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. RESULTS: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). CONCLUSIONS: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

Linear dichroism and optical anisotropy of silver nanoprisms in polymer films.

We present optical studies of two different size distributions of silver triangular nanoprisms, one with a dipole resonance at 520 nm and the other with a dipole resonance at 650 nm, placed in different media. Significant wavelength-dependent depolarization of scattered light from the silver nanoprisms suspended in water indicates strong interference of multiple surface plasmon resonant modes in the same particle. We use this depolarization as a probe of light scattering by the nanoprisms in a lipid solution due to the rejection of a polarized background scattering. Also, the silver nanoprisms were embedded in a polyvinyl alcohol polymer matrix and oriented by stretching the polymer/nanoprism nanocomposite films. We observe significantly increased linear dichroism in the region associated with the plasmonic in-plane dipole mode upon stretching. Additionally, there is a weaker linear dichroism in the region associated with out-of-plane modes, which vanish in the extinction spectrum of the stretched nanocomposite film.

[Phenotypic and genotypic detection of the production of carbapenemases type NDM-1 and KPC in isolated Enterobacteriaceae in a clinical laboratory in Maracay, Venezuela]. / Detección fenotípica y genotípica de la producción de carbapenemasas tipo NDM-1 y KPC en enterobacterias aisladas en un laboratorio clínico en Maracay, Venezuela.

BACKGROUND: The production of carbapenem-hydrolyzing ß-lactamases is one of the most concerning resistance mechanisms since it eliminates the last therapeutic option against multidrug resistant microorganisms. AIM: To determine the production of KPC and NDM-1 type carbapenemases, using phenotypic and genotypic methods, in isolated enterobacteria in a clinical laboratory in the city of Maracay, Venezuela. METHODS: The production of carbapenemases was determined by phenotypic (according to the Malbrán algorithm) and genotypic methods (amplification of the blaNDM-1 and blaKPC genes by PCR) in clinical isolates of Enterobacteriaceae during the period March-August 2018. RESULTS: 605 Enterobacteriaceae of different species were identified, being Escherichia coli the strain with the highest percentage of isolation (61.3%), followed by Klebsiella pneumoniae (14.9%). Sixteen strains (2.64%) were positive for carbapenemases production: 13 strains of K. pneumoniae and three of the Enterobacter cloacae complex. PCR showed that 14 strains (87.5%) carry the blaNDM-1 gene and two strains (12.5%) the blaKPC gene; 100% agreement was observed between phenotypic determination and PCR for both groups of enzymes. CONCLUSIONS: The results of this study showed a higher incidence of metallo-ß-lactamase type NDM-1, which rapid dissemination and consequently difficult control has been cause of epidemiological alert. The identification of the type of enzyme would allow establishing more accurate management and control strategies in order to eradicate these pathogens.

Reaction strategies for the enzymatic synthesis of neopentyl glycol diheptanoate.

This work describes for the first time the green synthesis of neopentyl glycol diheptanoate in a solvent-free medium via an enzymatic pathway. The process has been carried out in an open-air reactor in order to ease water removal through evaporation and shift the chemical equilibrium towards product formation. The inhibiting effect of high concentrations of heptanoic acid has been put into evidence by a reduction of initial reaction rate when esterification was performed with stoichiometric amounts of substrates. Therefore, in this work different strategies for the stepwise addition of heptanoic acid are proposed, and best results were obtained when stoichiometric quantities of acid were divided in four equal amounts and added when previous batch was consumed. Biocatalyst Novozym® 435 concentration and temperature were optimised, giving yields of 90% in neopentyl glycol diheptanoate when 7.5% (w/w) and 70 °C were used. With a remaining 7% of heptanoic acid (probably caused by the alcohol evaporation) the addition of neopentyl glycol led to a conversion of 95%. Thus, product can be used in cosmetics without further purification and can be labelled as environmentally-friendly synthesized because of its enzymatic origin.

No Difference in Myosin Kinetics and Spatial Distribution of the Lever Arm in the Left and Right Ventricles of Human Hearts.

The systemic circulation offers larger resistance to the blood flow than the pulmonary system. Consequently, the left ventricle (LV) must pump blood with more force than the right ventricle (RV). The question arises whether the stronger pumping action of the LV is due to a more efficient action of left ventricular myosin, or whether it is due to the morphological differences between ventricles. Such a question cannot be answered by studying the entire ventricles or myocytes because any observed differences would be wiped out by averaging the information obtained from trillions of myosin molecules present in a ventricle or myocyte. We therefore searched for the differences between single myosin molecules of the LV and RV of failing hearts In-situ. We show that the parameters that define the mechanical characteristics of working myosin (kinetic rates and the distribution of spatial orientation of myosin lever arm) were the same in both ventricles. These results suggest that there is no difference in the way myosin interacts with thin filaments in myocytes of failing hearts, and suggests that the difference in pumping efficiencies are caused by interactions between muscle proteins other than myosin or that they are purely morphological.

Drug-Induced Lung Injury in a Liver Transplant Patient Treated With Sofosbuvir.

New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015. Regimens were as follows: sofosbuvir+simeprevir (8), SOF+ledipasvir (6), sofosbuvir+daclatasvir (5) and sofosbuvir+ribavirin (5). Overall, treatment was very well tolerated with only mild adverse events in 42% of patients. However, a 52-year-old woman developed severe respiratory failure within 10 days after beginning sofosbuvir+daclatasvir. High-resolution computerized tomography showed areas of diffused ground-glass opacities in both lungs, suggesting drug-induced lung injury. The bronchoalveolar lavage showed marked signs of acute inflammation without recovering any infectious agent. The patient was treated with high-dose corticosteroids and steadily recovered. DAA therapy was not discontinued, but sofosbuvir was replaced by simeprevir. She reached sustained virologic response after completing 24 weeks of DAA therapy. Given the close temporal association, radiologic and bronchoalveolar lavage findings, and negative work-up for infectious agents, we postulated that sofosbuvir was the most likely explanation for drug-induced lung injury in our patient.

Detección fenotípica y genotípica de la producción de carbapenemasas tipo NDM-1 y KPC en enterobacterias aisladas en un laboratorio clínico en Maracay, Venezuela / Phenotypic and genotypic detection of the production of carbapenemases type NDM-1 and KPC in isolated Enterobacteriaceae in a clinical laboratory in Maracay, Venezuela

INTRODUCCIÓN: La producción de beta-lactamasas capaces de hidrolizar a los carbapenémicos es uno de los mecanismos de resistencia más preocupantes porque eliminan la última opción terapéutica frente a los microorganismos multi-resistentes. OBJETIVO: Determinar la producción de carbapenemasas tipo KPC y NDM-1, empleando métodos fenotípicos y genotípicos, en enterobacterias aisladas en un laboratorio clínico de la ciudad de Maracay, Venezuela. MÉTODOS: Se determinó la producción de carbapenemasas mediante métodos fenotípicos (según algoritmo de Malbrán) y genotípicos (amplificación de los genes blaNDM-1 y blaKPC por RPC) en enterobacterias aisladas en un laboratorio clínico durante el período marzo-agosto 2018. RESULTADOS: Se identificaron 605 enterobacterias de diferentes especies, siendo Escherichia coli la cepa con mayor porcentaje de aislamiento (61,3%), seguida por Klebsiella pneumoniae (14,9%). Diez y seis enterobacterias (2,64%) fueron positivas para la producción de carbapenemasas: 13 cepas de K. pneumoniae y tres del complejo Enterobacter cloacae. La RPC demostró que 14 cepas (87,5%) contienen el gen blaNDM-1 y dos (12,5%) el gen blaKPC; se observó 100% de concordancia entre la determinación fenotípica y la RPC para ambos grupos de enzimas. CONCLUSIONES: Los resultados mostraron mayor incidencia de la metalo-beta-lactamasa tipo NDM-1, reconocida como una alarma epidemiológica debido a que su rápida diseminación dificulta su control, por lo que la identificación del tipo de enzima permitiría establecer estrategias de manejo y control más certeras con la finalidad de erradicar a dichos patógenos.

BACKGROUND: The production of carbapenem-hydrolyzing beta-lactamases is one of the most concerning resistance mechanisms since it eliminates the last therapeutic option against multidrug resistant microorganisms. AIM: To determine the production of KPC and NDM-1 type carbapenemases, using phenotypic and genotypic methods, in isolated enterobacteria in a clinical laboratory in the city of Maracay, Venezuela. METHODS: The production of carbapenemases was determined by phenotypic (according to the Malbrán algorithm) and genotypic methods (amplification of the blaNDM-1 and blaKPC genes by PCR) in clinical isolates of Enterobacteriaceae during the period March-August 2018. RESULTS: 605 Enterobacteriaceae of different species were identified, being Escherichia coli the strain with the highest percentage of isolation (61.3%), followed by Klebsiella pneumoniae (14.9%). Sixteen strains (2.64%) were positive for carbapenemases production: 13 strains of K. pneumoniae and three of the Enterobacter cloacae complex. PCR showed that 14 strains (87.5%) carry the blaNDM-1 gene and two strains (12.5%) the blaKPC gene; 100% agreement was observed between phenotypic determination and PCR for both groups of enzymes. CONCLUSIONS: The results of this study showed a higher incidence of metallo-beta-lactamase type NDM-1, which rapid dissemination and consequently difficult control has been cause of epidemiological alert. The identification of the type of enzyme would allow establishing more accurate management and control strategies in order to eradicate these pathogens.

Organochlorinated pesticides in sediments from the Lake Albufera of Valencia (Spain).

Bottom sediment samples from 121 sites of the Lake Albufera of Valencia were analyzed. Dieldrin, endrin, heptachlor and op'-DDT were not detected (<0.01 ng g(-1)) in 88-93% of the sites. Aldrin and HCB concentration ranges were between <0.01 and 0.1 ng g(-1) in 86% and 94% of the sites, respectively. Heptachlor-epoxide and lindane 95% confidence intervals were 0.2-0.5 and 0.06-0.12, respectively. The greatest average concentration corresponds to pp'-DDE, pp'-DDD and pp'-DDT. The sum of six isomers and derivatives of the DDT average concentration reaches 2.1 ng g(-1), as opposed to 2.7 ng g(-1) for the sum of 13 pesticides considered. In the site with a major contamination, 27.0 ng g(-1) of pp'-DDD and 12.8 ng g(-1) of pp'-DDT were accumulated. The DDE:DDT proportion average was 0.37, indicating an aged DDT contamination. Concentrations of pesticides in sediments were compared to three sediment quality guidelines, and indicated that a low biological effects level can be expected in either sediments or aquatic organisms.

Au Lα x-rays induced by photons from 241Am: Comparison of experimental results and the predictions of PENELOPE.

The results of experiments performed, measuring the Lα x-rays emitted by Au due to excitation by photons of various energies from an (241)Am sample at forward-scattered angles in the range 0° to 65°, are compared to the predictions of the Monte Carlo code, PENELOPE. The experimental data are in good agreement with the predictions of the program. A comparison of the angular distributions of the probability densities (as predicted by the program) related to the Au Lα and Lß x-rays suggests that PENELOPE does not simulate the phenomena described by Flügge et al. (1972).