Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality

OBJECTIVE: To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. DESIGN: Prospective observational cohort study. METHODS: Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. RESULTS: Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. CONCLUSION: Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Proporción de carga asistencial generada por la diabetes mellitus en las consultas de enfermería de atención primaria de salut

Objetivo La mayoría de enfermos con diabetes mellitus tipo 2 (DM2) se controla en atención primaria de salud (APS). La atención y educación proporcionadas por enfermería son clave para controlar la glucemia y prevenir las complicaciones macro y microangiopáticas de la DM. El objetivo de este trabajo es conocer la proporción de carga asistencial atribuible a la DM en consultas de enfermería de APS. Material y método Estudio observacional, analítico y transversal. Durante 2 semanas consecutivas se registraron datos de todos los enfermos que acudieron a 15 consultas de enfermería de APS ubicadas en 14 Áreas Básicas de Salud (ABS) de la provincia de Barcelona. Las variables de estudio fueron: edad, sexo, situación laboral, motivo de consulta, duración de la visita, presencia de DM y, en los enfermos diabéticos, el tipo de tratamiento. La recogida de datos se realizó en 2 períodos. El primero entre noviembre del año 2003 y enero del 2004 y el segundo en abril de 2005. Se realizó un análisis descriptivo de estas variables con un intervalo de confianza del 95% y la asociación entre variables mediante el programa SPSS v.11.1. Resultados Tenía DM el 29% de los pacientes. La DM es el primer motivo de consulta (29,1%), aumenta con la edad y llega al 40% en mayores de 65 años. La duración media de una visita por DM es de 14,59 min, un 30,8% más elevada que la duración media del resto de los problemas de salud. Globalmente, las mujeres consultan más que los varones (56,6%) excepto en DM, curas y hábito tabáquico. Conclusiones La DM es el problema de salud que genera más demanda y consume más tiempo de enfermería en la APS. Esta realidad y el futuro que se prevé con relación al incremento de la prevalencia de DM exigen considerar nuevas estrategias organizativas y formativas, y establecer criterios para mejorar la gestión de recursos y promover estrategias educativas más efectivas.

Proporción de carga asistencial generada por la diabetes mellitus en las consultas de enfermería de atención primaria de salut

Objetivo La mayoría de enfermos con diabetes mellitus tipo 2 (DM2) se controla en atención primaria de salud (APS). La atención y educación proporcionadas por enfermería son clave para controlar la glucemia y prevenir las complicaciones macro y microangiopáticas de la DM. El objetivo de este trabajo es conocer la proporción de carga asistencial atribuible a la DM en consultas de enfermería de APS. Material y método Estudio observacional, analítico y transversal. Durante 2 semanas consecutivas se registraron datos de todos los enfermos que acudieron a 15 consultas de enfermería de APS ubicadas en 14 Áreas Básicas de Salud (ABS) de la provincia de Barcelona. Las variables de estudio fueron: edad, sexo, situación laboral, motivo de consulta, duración de la visita, presencia de DM y, en los enfermos diabéticos, el tipo de tratamiento. La recogida de datos se realizó en 2 períodos. El primero entre noviembre del año 2003 y enero del 2004 y el segundo en abril de 2005. Se realizó un análisis descriptivo de estas variables con un intervalo de confianza del 95% y la asociación entre variables mediante el programa SPSS v.11.1. Resultados Tenía DM el 29% de los pacientes. La DM es el primer motivo de consulta (29,1%), aumenta con la edad y llega al 40% en mayores de 65 años. La duración media de una visita por DM es de 14,59 min, un 30,8% más elevada que la duración media del resto de los problemas de salud. Globalmente, las mujeres consultan más que los varones (56,6%) excepto en DM, curas y hábito tabáquico. Conclusiones La DM es el problema de salud que genera más demanda y consume más tiempo de enfermería en la APS. Esta realidad y el futuro que se prevé con relación al incremento de la prevalencia de DM exigen considerar nuevas estrategias organizativas y formativas, y establecer criterios para mejorar la gestión de recursos y promover estrategias educativas más efectivas.

La función activadora de un apósito bioactivo con carga iónica sobre los fibroblastos humanos

La cicatrización de las heridas es un proceso complejo que implica diferentes fases que se solapan entre sí, incluyendo la inflamación, la epitelización, la angiognesis y la síntesis y deposición de matriz extracelular. Los fibroblastos dérmicos tienen una función esencial en la formación del tejido de granulación. Migran hasta la lesión en respuesta a citoquinas, proliferan y sintetizan las proteínas de la matriz extracelular, las cuales son la base del proceso de reparación futuro. Los oligoelementos tales como el zinc y el manganeso son necesarios para muchas funciones celulares y, por consiguiente, pueden potencialmente estimular los procesos de reparación de las heridas. En el presente estudio hemos investigado el efecto de un aposito que contiene zinc, calcio y manganeso (Trionic®) sobre la proliferación, el crecimiento, la síntesis de colágeno I y III y la migración de los fibroblastos. Los resultados obtenidos indican que los oligoelementos solubles presentes en Trionic® actúan estimulando la proliferación, el crecimiento, la biosíntesis de colágeno y la migración de los fibroblastos. Dada la participación crucial que estas funciones celulares tienen sobre el comportamiento de los fibroblastos durante el proceso de formación del tejido de granulación, concluimos que los iones Ca2+, Zn2+, y Mn2+ contenidos en Trionic® pueden proporcionar potenciales beneficios en el tratamiento de las heridas crónicas y durante la fase reparativa del proceso de cicatrización.

HIV-1 Capture and Transmission by Dendritic Cells: The Role of Viral Glycolipids and the Cellular Receptor Siglec-1

Dendritic cells (DCs) are essential in order to combat invading viruses and trigger antiviral responses. Paradoxically, in the case of HIV-1, DCs might contribute to viral pathogenesis through trans-infection, a mechanism that promotes viral capture and transmission to target cells, especially after DC maturation. In this review, we highlight recent evidence identifying sialyllactosecontaining gangliosides in the viral membrane and the cellular lectin Siglec-1 as critical determinants for HIV-1 capture and storage by mature DCs and for DC-mediated trans-infection of T cells. In contrast, DC-SIGN, long considered to be the main receptor for DC capture of HIV-1, plays a minor role in mature DC-mediated HIV-1 capture and trans-infection.

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Identification of CD8+ cytotoxic T lymphocyte (CTL) epitopes has traditionally relied upon testing of overlapping peptide libraries for their reactivity with T cells in vitro. Here, we pursued deep ligand sequencing (DLS) as an alternative method of directly identifying those ligands that are epitopes presented to CTLs by the class I human leukocyte antigens (HLA) of infected cells. Soluble class I HLA-A*11:01 (sHLA) was gathered from HIV-1 NL4-3-infected human CD4+ SUP-T1 cells. HLA-A*11:01 harvested from infected cells was immunoaffinity purified and acid boiled to release heavy and light chains from peptide ligands that were then recovered by size-exclusion filtration. The ligands were first fractionated by high-pH high-pressure liquid chromatography and then subjected to separation by nano-liquid chromatography (nano-LC)–mass spectrometry (MS) at low pH. Approximately 10 million ions were selected for sequencing by tandem mass spectrometry (MS/MS). HLA-A*11:01 ligand sequences were determined with PEAKS software and confirmed by comparison to spectra generated from synthetic peptides. DLS identified 42 viral ligands presented by HLA-A*11:01, and 37 of these were previously undetected. These data demonstrate that (i) HIV-1 Gag and Nef are extensively sampled, (ii) ligand length variants are prevalent, particularly within Gag and Nef hot spots where ligand sequences overlap, (iii) noncanonical ligands are T cell reactive, and (iv) HIV-1 ligands are derived from de novo synthesis rather than endocytic sampling. Next-generation immunotherapies must factor these nascent HIV-1 ligand length variants and the finding that CTL-reactive epitopes may be absent during infection of CD4+ T cells into strategies designed to enhance T cell immunity.

Transporte de carga em compósitos de polianilina/V2O5

In this work, composites formed from a mixture of V2O5 and polyaniline (PANI) were investigated, for applications as cathode materials for secondary lithium batteries. Electrochemical quartz crystal microbalance (EQCM) data show that charge compensation in the [PANI]0.3V2O5 nanocomposite is achieved predominantly by Li+ migration. However, the charge compensation in the [PANI]V2O5 microcomposite occurs by Li+ and ClO4- transport. Electrochemical Impedance Spectroscopy (EIS) measurements reveal several benefits of nanohybrid formation, including the achievement of shorter ionic diffusion pathways, the higher diffusion rate of the lithium ion and also the higher electronic conductivity, which are responsible for a synergetic effect of the energy storage properties.

Relação entre transferência de carga e as interações intermoleculares em complexos de hidrogênio heterocíclicos

Hydrogen-bonded complexes formed by the interaction of the heterocyclic molecules C2H4O and C2H5N with HF, HCN, HNC and C2H2 have been studied using density functional theory. The hydrogen bond strength has been analyzed through electron density charge transfer from the proton acceptor to the proton donor. The density charge transfer has been estimated using different methods such as Mulliken population analysis, CHELPG, GAPT and AIM. It has been shown that AIM-estimated charge transfer correlates very well with the hydrogen bond energy and the infrared bathochromic effect of the proton donor stretching frequencies.

HIV-1 immune activation induces siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells

Background: Myeloid cells are key players in the recognition and response of the host against invading viruses. Paradoxically, upon HIV-1 infection, myeloid cells might also promote viral pathogenesis through trans-infection, a mechanism that promotes HIV-1 transmission to target cells via viral capture and storage. The receptor Siglec-1 (CD169) potently enhances HIV-1 trans-infection and is regulated by immune activating signals present throughout the course of HIV-1 infection, such as interferon α (IFNα). Results: Here we show that IFNα-activated dendritic cells, monocytes and macrophages have an enhanced ability to capture and trans-infect HIV-1 via Siglec-1 recognition of viral membrane gangliosides. Monocytes from untreated HIV-1-infected individuals trans-infect HIV-1 via Siglec-1, but this capacity diminishes after effective antiretroviral treatment. Furthermore, Siglec-1 is expressed on myeloid cells residing in lymphoid tissues, where it can mediate viral trans-infection. Conclusions: Siglec-1 on myeloid cells could fuel novel CD4+ T-cell infections and contribute to HIV-1 dissemination in vivo.

Implementação computacional do modelo carga-fluxo de carga-fluxo de dipolo para cálculo e interpretação das intensidades do espectro infravermelho

The first computational implementation that automates the procedures involved in the calculation of infrared intensities using the charge-charge flux-dipole flux model is presented. The atomic charges and dipoles from the Quantum Theory of Atoms in Molecules (QTAIM) model was programmed for Morphy98, Gaussian98 and Gaussian03 programs outputs, but for the ChelpG parameters only the Gaussian programs are supported. Results of illustrative but new calculations for the water, ammonia and methane molecules at the MP2/6-311++G(3d,3p) theoretical level, using the ChelpG and QTAIM/Morphy charges and dipoles are presented. These results showed excellent agreement with analytical results obtained directly at the MP2/6-311++G(3d,3p) level of theory.

Determinação espectrofotométrica de cefalexina em formulações farmacêuticas explorando a sua reação de transferência de carga com a quinalizarina

This work proposes a new simple and fast spectrophotometric method for cephalexin determination in pharmaceutical formulations. The method is based on the charge transfer reaction between cephalexin and quinalizarin in dimethylsulfoxide medium. Several analytical parameters related to the system were optimized and the reaction was characterized in terms of stoichiometry. Also, association constant and apparent molar absorptivity of the product were determined. The method presented a limit of detection of 0.46 mg L-1 and a quantification limit of 1.5 mg L-1. It was successfully applied in the determination of cephalexin in two samples of commercial pharmaceutical formulations.

Garlic viral complex: identification of Potyviruses and Carlavirus in Central Brazil

Garlic viruses often occur in complex infections in nature. In this study, a garlic virus complex, collected in fields in Brazil, was purified. RT-PCR was performed using specific primers designed from the consensus regions of the coat protein genes of Onion yellow dwarf virus, a garlic strain (OYDV-G) and Leek yellow stripe virus (LYSV). cDNA of Garlic common latent virus (GCLV) was synthesized using oligo-dT and random primers. By these procedures individual garlic virus genomes were isolated and sequenced. The nucleotide sequence analysis associated with serological data reveals the presence of two Potyvirus OYDV-G and LYSV, and GCLV, a Carlavirus, simultaneously infecting garlic plants. Deduced amino acid sequences of the Brazilian isolates were compared with related viruses reported in different geographical regions of the world. The analysis showed closed relations considering the Brazilian isolates of OYDV-G and GCLV, and large divergence considering LYSV isolate. The detection of these virus species was confirmed by specific reactions observed when coat protein genes of the Brazilian isolates were used as probes in dot-blot and Southern blot hybridization assays. In field natural viral re-infection of virus-free garlic was evaluated.