HIV-1 protease mutation 82M contributes to phenotypic resistance to protease inhibitors in subtype G.

OBJECTIVES: The purpose of this study was the qualitative and quantitative assessment of the in vitro effect of HIV-1 protease (PR) mutation 82M on replication capacity and susceptibility to the eight clinically available PR inhibitors (PIs). METHODS: The 82M substitution was introduced by site-directed mutagenesis in wild-type subtype B and G strains, as well as reverted back to wild-type in a therapy-failing strain. The recombinant viruses were evaluated for their replication capacity and susceptibility to PIs. RESULTS: The single 82M mutation within a wild-type subtype B or G background did not result in drug resistance. However, the in vitro effect of single PR mutations on PI susceptibility is not always distinguishable from wild-type virus, and particular background mutations and polymorphisms are required to detect significant differences in the drug susceptibility profile. Consequently, reverting the 82M mutation back to wild-type (82I) in a subtype G isolate from a patient that failed therapy with multiple other PR mutations did result in significant increases in susceptibility towards indinavir and lopinavir and minor increases in susceptibility towards amprenavir and atazanavir. The presence of the 82M mutation also slightly decreased viral replication, whether it was in the genetic background of subtype B or subtype G. CONCLUSIONS: Our results suggest that 82M has an impact on PI susceptibility and that this effect is not due to a compensatory effect on the replication capacity. Because 82M is not observed as a polymorphism in any subtype, these observations support the inclusion of 82M in drug resistance interpretation systems and PI mutation lists.

Comparison of the COBAS TAQMAN HIV-1 HPS with VERSANT HIV-1 RNA 3.0 assay (bDNA) for plasma RNA quantitation in different HIV-1 subtypes.

Quantitation of HIV-1 RNA levels in plasma has an undisputed prognostic value and is extremely important for evaluating response to antiretroviral therapy. The purpose of this study was to evaluate the performance of the real-time PCR COBAS TaqMan 48 analyser, comparing it to the existing VERSANT 3.0 (bDNA) for HIV-1 RNA quantitation in plasma of individuals infected with different HIV-1 subtypes (104 blood samples). A positive linear correlation between the two tests (r2 = 0.88) was found. Quantitation by the COBAS TaqMan assay was approximately 0.32log10 higher than by bDNA. The relationship between the two assays was similar within all subtypes with a Deming regression of <1 and <0 for the Bland-Altman plots. Overall, no significant differences were found in plasma viral load quantitation in different HIV-1 subtypes between both assays; therefore these assays are suitable for viral load quantitation of highly genetically diverse HIV-1 plasma samples.

Profile of intoxications served at the 24-hour emergency service unit

Intoxications represent a serious public health problem. According to the World Health Organization, 193,000 deaths per year are caused by unintended intoxications worldwide. This study aims to know the profile of intoxications at the 24-hour Emergency Service Unit in Divinópolis, in the state of Minas Gerais. This is a descriptive study in which the study population chosen were all patients treated for intoxications in the period from 2017 to 2018, registered in the health service; 421 cases of intoxications were recorded. The female gender was the most prevalent, and the age group with the most cases was 21 to 30 years. The main circumstance found was attempted suicide (83.1%), and the main causative agent was drugs (76.5%), with benzodiazepines being the main class responsible for intoxications. The most used treatment was gastric lavage and activated charcoal. This study demonstrates that knowledge about the city's intoxication profile is important for the development of treatment and patient management methods to better suit the demands of the municipality.

Sentidos das oficinas terapêuticas ocupacionais do CAPS no cotidiano dos usuários: uma descrição fenomenológica / Senses of CAPS therapeutic activities in the daily life users: a phenomenological description / Significados de las actividades terapéuticas de lo CAPS en la vida diária de los usuários: una descripción fenomenológica

O objetivo deste artigo é o de apresentar os resultados da investigação realizada no Centro de Atenção Psicossocial (CAPS) da cidade de Unaí, na qual se buscou conhecer a percepção dos usuários acerca dos sentidos das atividades terapêuticas ocupacionais em seu cotidiano, buscando o seu ponto de vista na constituição dos sentidos dessa participação. Pretende-se nele descrever fenomenologicamente o relato dos participantes. Além da observação empírica, essa pesquisa apoia-se em uma referência bibliográfica que evidencia o estatuto da loucura no mundo atual e a forma como a psiquiatria pretende tratá-la. Entre tais referências, está a história da loucura e do processo de transformação da loucura em doença mental, e como esta se tornou objeto do código médico. Os relatos dos participantes sobre suas vivências cotidianas da loucura evidenciam que eles têm muito a dizer sobre seu universo, assim como sobre a relação entre razão e loucura.

The objective of this paper is to present results of the research carried out at the Psychosocial Care Center (CAPS) of City of Unaí-MG, in which we sought to know the users' perception about meanings of occupational therapeutic activities in their daily life, seeking their point of view in the constitution of meanings of this participation. It intends to describe in it phenomenologically report of the participants. In addition to empirical observation, this research is based on a critical bibliographical reference regarding the status of madness in the present world and the way Psychiatry intends to treat it. Among such references is the history of madness as the process of transforming madness into mental illness, and how it became object of medical code. The participants' reports of their everyday experiences of madness, show that they have much to say about their universe, as well as about the relationship between reason and madness.

El propósito de este artículo es presentar los resultados de la investigación llevada a cabo em el Centro de Atención Psicosocial (CAPS) de la ciudad de Unaí, que tenía como objetivo conocer la percepción de los usuarios acerca de los significados de las actividades terapéuticas ocupacionales en su vida diaria, en busca de su punto de vista la constitución de los sentidos que la participación. El objetivo describir fenomenológicamente a los participantes. Además de la observación empírica, le apoyamos en una referencia bibliográfica en relación con la locura de estatus en el mundo de hoy y cómo la psiquiatría tiene la intención de tratarlo. Entre estas referencias, es la historia de la locura el proceso de transformación de la locura en la enfermedad mental, y cómo se convirtió en el objeto del código médica. Los informes de los participantes sobre sus experiencias diarias de mostrar la locura que tienen mucho que decir sobre su universo, así como sobre la relación entre la razón y la locura.

Effect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and G.

Europe is currently observing a significant rise in non-B subtypes. Consequently, the effect of genetic variability on therapy response or genotypic resistance interpretation algorithms is an emerging concern. The purpose of this study is to investigate the amino acid substitutions selected under drug pressure in the protease of human immunodeficiency virus type 1 (HIV-1) subtypes B and G, and determine if there are any significant differences. We investigated therapy-related and subtype-related substitutions in the protease, considering subtype, overall protease inhibitor treatment and individual drug exposure. Many mutations were significantly related to protease inhibitor (PI) therapy, with mutations exclusive to subtype B or subtype G. Some mutations are at positions related to resistance in both subtypes, but the amino acid substitution is different. Other mutations were significantly associated with subtype and PI selective pressure (p<0.05), pointing towards a differential selective pressure in both subtypes. We confirmed previous reports on the subtype-dependent selection of D30N and 89I, and identified a new mutation with such differential selective pressure: 37D was preferentially selected by lopinavir in subtype B. Other novel mutations found under therapy pressure were 13A, 35N, K55R, I66F, I72L/T, T74S, 82M and 89I/V. Our study indicates that even though in general, drug selective pressure and resistance pathways are relatively similar between subtypes B and G, some differences do occur, leading to subtype-dependent substitutions.