Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients

BACKGROUND: Efavirenz (EFV) and nevirapine (NVP) are metabolized by cytochrome P450 2B6 (CYP2B6). Allele 516 G>T (Gln172His) is associated with diminished activity of this isoenzyme, and may lead to differences in drug exposure. METHODS: We evaluated this allele as a pharmacogenetic marker of EFV and NVP pharmacokinetics and EFV toxicity in 167 participants receiving EFV and 59 receiving NVP recruited within the genetics project of the Swiss HIV Cohort Study. Drug concentrations were measured in plasma and in peripheral blood mononuclear cells (PBMCs) from the same sample. Neuropsychological toxicity of EFV (sleep disorders, mood disorders, fatigue) was assessed using a standardized questionnaire. RESULTS AND CONCLUSIONS: CYP2B6 516TT was associated with greater plasma and intracellular exposure to EFV, and greater plasma exposure to NVP. Intracellular drug concentration, and CYP2B6 genotype were predictors of EFV neuropsychological toxicity. CYP2B6 genotyping may be useful to complement an individualization strategy based on plasma drug determinations to increase the safety and tolerability of EFV.

Changes in German sport participation

Sport has become a highly differentiated social phenomenon in recent years. Changes in society, such as individualization, the growing significance of the health and body culture, and changing values, are considered to be generative mechanisms for increasing social importance and the differentiation of modern sport. Although discussions in sport sociology attribute the changes observed in recent decades of sport participation to a socially determined differentiation of sport, this premise has hardly ever been empirically tested. The present study examines to what extent the postulated developments in sport can be observed on the micro level of those engaging in sport, by examining sport behaviour from a contemporary historical perspective. Based on a life-course approach to research, a total of 1739 over 50-year-olds in Germany were asked about their sport participation as part of a retrospective longitudinal study. Results show that the increasing differentiation of sport can be documented by more diversified forms of individual sport careers. During a 30-year observation period the popularity of competitive sport decreased and the variety of ways in which sport was organized increased. A differentiated analysis based on examining three birth cohorts showed that the reported change in sport participation can be attributed to age, cohort and period effects. In addition, the present study examines how specific events in contemporary history are reflected in individual sporting careers. Sport careers in Chemnitz (Eastern Germany) and Braunschweig (Western Germany) differed before German reunification, but these differences have evened out after the political changes and the process of transformation.

Adaptive Algorithms for Personalized Diabetes Treatment

Dynamic systems, especially in real-life applications, are often determined by inter-/intra-variability, uncertainties and time-varying components. Physiological systems are probably the most representative example in which population variability, vital signal measurement noise and uncertain dynamics render their explicit representation and optimization a rather difficult task. Systems characterized by such challenges often require the use of adaptive algorithmic solutions able to perform an iterative structural and/or parametrical update process towards optimized behavior. Adaptive optimization presents the advantages of (i) individualization through learning of basic system characteristics, (ii) ability to follow time-varying dynamics and (iii) low computational cost. In this chapter, the use of online adaptive algorithms is investigated in two basic research areas related to diabetes management: (i) real-time glucose regulation and (ii) real-time prediction of hypo-/hyperglycemia. The applicability of these methods is illustrated through the design and development of an adaptive glucose control algorithm based on reinforcement learning and optimal control and an adaptive, personalized early-warning system for the recognition and alarm generation against hypo- and hyperglycemic events.

An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy

Prostate cancer (CaP) is the most commonly diagnosed malignancy in males in the Western world with one in six males diagnosed in their lifetime. Current clinical prognostication groupings use pathologic Gleason score, pre-treatment prostatic-specific antigen and Union for International Cancer Control-TNM staging to place patients with localized CaP into low-, intermediate- and high-risk categories. These categories represent an increasing risk of biochemical failure and CaP-specific mortality rates, they also reflect the need for increasing treatment intensity and justification for increased side effects. In this article, we point out that 30-50% of patients will still fail image-guided radiotherapy or surgery despite the judicious use of clinical risk categories owing to interpatient heterogeneity in treatment response. To improve treatment individualization, better predictors of prognosis and radiotherapy treatment response are needed to triage patients to bespoke and intensified CaP treatment protocols. These should include the use of pre-treatment genomic tests based on DNA or RNA indices and/or assays that reflect cancer metabolism, such as hypoxia assays, to define patient-specific CaP progression and aggression. More importantly, it is argued that these novel prognostic assays could be even more useful if combined together to drive forward precision cancer medicine for localized CaP.

Enhancing Food Sovereignty and Food Security through the Revitalization of Indigenous Knowledge: Experiences from the Bolivian Andes

Endogenous development is defined as development that values primarily locally available resources and the way people organized themselves for that purpose. It is a dynamic and evolving concept that also embraces innovations and complementation from other than endogenous sources of knowledge; however, only as far as they are based on mutual respect and the recognition of cultural and socioeconomic self-determination of each of the parties involved. Experiences that have been systematized in the context of the BioAndes Program are demonstrating that enhancing food security and food sovereignty on the basis of endogenous development can be best achieved by applying a ‘biocultural’ perspective: This means to promote and support actions that are simultaneously valuing biological (fauna, flora, soils, or agrobiodiversity) and sociocultural resources (forms of social organization, local knowledge and skills, norms, and the related worldviews). In Bolivia, that is one of the Latin-American countries with the highest levels of poverty (79% of the rural population) and undernourishment (22% of the total population), the Program BioAndes promotes food sovereignty and food security by revitalizing the knowledge of Andean indigenous people and strengthening their livelihood strategies. This starts by recognizing that Andean people have developed complex strategies to constantly adapt to highly diverse and changing socioenvironmental conditions. These strategies are characterized by organizing the communities, land use and livelihoods along a vertical gradient of the available eco-climatic zones; the resulting agricultural systems are evolving around the own sociocultural values of reciprocity and mutual cooperation, giving thus access to an extensive variety of food, fiber and energy sources. As the influences of markets, competition or individualization are increasingly affecting the life in the communities, people became aware of the need to find a new balance between endogenous and exogenous forms of knowledge. In this context, BioAndes starts by recognizing the wealth and potentials of local practices and aims to integrate its actions into the ongoing endogenous processes of innovation and adaptation. In order to avoid external impositions and biases, the program intervenes on the basis of a dialogue between exogenous, mainly scientific, and indigenous forms of knowledge. The paper presents an analysis of the strengths and weaknesses of enhancing endogenous development through a dialogue between scientific and indigenous knowledge by specifically focusing on its effects on food sovereignty and food security in three ‘biocultural’ rural areas of the Bolivian highlands. The paper shows how the dialogue between different forms of knowledge evolved alongside the following project activities: 1) recuperation and renovation of local seeds and crop varieties (potato – Solanum spp., quinoa – Chenopodium quinoa, cañahua – Chenopodium pallidicaule); 2) support for the elaboration of community-based norms and regulations for governing access and distribution of non-timber forest products, such as medicinal, fodder, and construction plants; 3) revitalization of ethnoveterinary knowledge for sheep and llama breeding; 4) improvement of local knowledge about the transformation of food products (sheep-cheese, lacayote – Cucurbita sp. - jam, dried llama meat, fours of cañahua and other Andean crops). The implementation of these activities fostered the community-based livelihoods of indigenous people by complementing them with carefully and jointly designed innovations based on internal and external sources of knowledge and resources. Through this process, the epistemological and ontological basis that underlies local practices was made visible. On this basis, local and external actors started to jointly define a renewed concept of food security and food sovereignty that, while oriented in the notions of well being according to a collectively re-crafted world view, was incorporating external contributions as well. Enabling and hindering factors, actors and conditions of these processes are discussed in the paper.

Evaluation of leaders – does gender still matter?

Purpose: Leadership positions are still stereotyped as male, especially in male-dominated fields such as STEM. Therefore, women in such positions run the risk of being evaluated less favorably than men. Our study investigates how female and male leaders in existing teams (engineering project) are evaluated, and how these evaluations change over time. Design/Methodology: Participants worked in 45 teams to develop specific engineering projects. Evaluations of 45 leaders (33% women) by 258 team members (39% women) were analyzed, that is, leaders’ self-evaluation and their evaluation by team members. Results: Although female and male leaders did not differ in their self-evaluations at the beginning of the project, female leaders evaluated themselves better within time. However, team members evaluated female leaders better than male leaders at the beginning of the project. These gender differences disappeared over the time. Limitations: It should be replicated in a non-student sample. Implications: The results show that female leaders entering a male-dominated field (engineering) are evaluated better by team members than male leaders at the beginning of the team work, in line with the ‘shifting standard model’ (Biernat & Fuegen, 2001). While the initial impression formation of female and male leaders is influenced by category membership, its impact decreases over time as a consequence of individualization (Fiske & Neuberg, 1990); this results in similar evaluations over time. Originality: To our knowledge this is the first study to systematically test perceptions of change in the evaluation over time of female and male leaders in natural setting.

Treatment Goals in Diabetes.

The quality of glycaemic control in diabetes mellitus relies on accurate individualization of available treatment options. Treatment targets depend on the type and duration of diabetes, the patients' abilities and characteristics and the individual risk for acute and/or late-stage complications. These complications include hypoglycaemia, which can be severe and life threatening, hyperglycaemia, which is a main factor for the development of cardiovascular disease, and macrovascular and microvascular disease, both of which are hallmark features of diabetes-associated constraints. Moreover, other treatment goals in diabetic patients influence both glycaemic control and quality of life. Lipoproteins, blood pressure, weight control, mental health and lifestyle are important factors that contribute to the frequency of diabetes-associated complications.

Biopoder en los cuerpos

En las últimas fechas, los estudios de biopolítica y biopoder se han elevado significativamente. Es un asunto antiguo, presente en la filosofía griega y en su realidad. Es la vieja discusión de la relación y la intromisión de la política en la vida y la superación del Estado de naturaleza. La actualidad de la biopolítica se refleja en las dimensiones que adquiere la tecnología y en el asedio de los poderes globales contra la democracia. El cuerpo humano, entidad visible y externa, resiente toda clase de intervenciones y sujeciones encaminadas a la individualización y al establecimiento de una realidad totalitaria. La Biopolítica y la Tanatopolítica se entrelazan al administrar la vida y la muerte en una realidad escalofriante donde la técnica introduce el artificio más allá de lo natural. El cuerpo humano como zona fronteriza de lo natural y lo artificial expresa los alcances del post-humanismo. Una cultura física más equilibrada ayudaría a contener la deshumanización tan extendida, que reduce y degrada lo corporal a la vez, mientras los poderes someten, discriminan, intervienen a través de cuerpos cada vez más dóciles

Biopoder en los cuerpos

En las últimas fechas, los estudios de biopolítica y biopoder se han elevado significativamente. Es un asunto antiguo, presente en la filosofía griega y en su realidad. Es la vieja discusión de la relación y la intromisión de la política en la vida y la superación del Estado de naturaleza. La actualidad de la biopolítica se refleja en las dimensiones que adquiere la tecnología y en el asedio de los poderes globales contra la democracia. El cuerpo humano, entidad visible y externa, resiente toda clase de intervenciones y sujeciones encaminadas a la individualización y al establecimiento de una realidad totalitaria. La Biopolítica y la Tanatopolítica se entrelazan al administrar la vida y la muerte en una realidad escalofriante donde la técnica introduce el artificio más allá de lo natural. El cuerpo humano como zona fronteriza de lo natural y lo artificial expresa los alcances del post-humanismo. Una cultura física más equilibrada ayudaría a contener la deshumanización tan extendida, que reduce y degrada lo corporal a la vez, mientras los poderes someten, discriminan, intervienen a través de cuerpos cada vez más dóciles

Biopoder en los cuerpos

En las últimas fechas, los estudios de biopolítica y biopoder se han elevado significativamente. Es un asunto antiguo, presente en la filosofía griega y en su realidad. Es la vieja discusión de la relación y la intromisión de la política en la vida y la superación del Estado de naturaleza. La actualidad de la biopolítica se refleja en las dimensiones que adquiere la tecnología y en el asedio de los poderes globales contra la democracia. El cuerpo humano, entidad visible y externa, resiente toda clase de intervenciones y sujeciones encaminadas a la individualización y al establecimiento de una realidad totalitaria. La Biopolítica y la Tanatopolítica se entrelazan al administrar la vida y la muerte en una realidad escalofriante donde la técnica introduce el artificio más allá de lo natural. El cuerpo humano como zona fronteriza de lo natural y lo artificial expresa los alcances del post-humanismo. Una cultura física más equilibrada ayudaría a contener la deshumanización tan extendida, que reduce y degrada lo corporal a la vez, mientras los poderes someten, discriminan, intervienen a través de cuerpos cada vez más dóciles

2D-Tasks for Cognitive Rehabilitation

Neuropsychological Rehabilitation is a complex clinic process which tries to restore or compensate cognitive and behavioral disorders in people suffering from a central nervous system injury. Information and Communication Technologies (ICTs) in Biomedical Engineering play an essential role in this field, allowing improvement and expansion of present rehabilitation programs. This paper presents a set of cognitive rehabilitation 2D-Tasks for patients with Acquired Brain Injury (ABI). These tasks allow a high degree of personalization and individualization in therapies, based on the opportunities offered by new technologies.

Class VI Unconventional Myosin is Required for Spermatogenesis in Drosophila

We have identified partial loss of function mutations in class VI unconventional myosin, 95F myosin, which results in male sterility. During spermatogenesis the germ line precursor cells undergo mitosis and meiosis to form a bundle of 64 spermatids. The spermatids remain interconnected by cytoplasmic bridges until individualization. The process of individualization involves the formation of a complex of cytoskeletal proteins and membrane, the individualization complex (IC), around the spermatid nuclei. This complex traverses the length of each spermatid resolving the shared membrane into a single membrane enclosing each spermatid. We have determined that 95F myosin is a component of the IC whose function is essential for individualization. In wild-type testes, 95F myosin localizes to the leading edge of the IC. Two independent mutations in 95F myosin reduce the amount of 95F myosin in only a subset of tissues, including the testes. This reduction of 95F myosin causes male sterility as a result of defects in spermatid individualization. Germ line transformation with the 95F myosin heavy chain cDNA rescues the male sterility phenotype. IC movement is aberrant in these 95F myosin mutants, indicating a critical role for 95F myosin in IC movement. This report is the first identification of a component of the IC other than actin. We propose that 95F myosin is a motor that participates in membrane reorganization during individualization.

Acampamento e assentamento rural como contexto de cuidado e educação compartilhados de crianças

Esta pesquisa se insere no campo da Psicologia Cultural do Desenvolvimento Humano e tem como objetivo investigar o compartilhamento da educação e do cuidado de crianças pequenas (1 a 5 anos) em um assentamento e um acampamento rural. Consideramos como compartilhamento da educação a participação de um grupo de pessoas, adultos ou crianças, nos momentos cotidianos da criança. A hipótese inicial da investigação estava relacionada a uma aparente coletivização da educação no acampamento e uma individualização no assentamento, determinados, sobretudo, pelas práticas culturais de cada contexto. Participaram da investigação 10 crianças (5 moradoras de um acampamento rural e 5 de um assentamento rural). A metodologia consistiu em observação participante com a imersão da pesquisadora por uma média de 6 dias no cotidiano familiar e comunitário de cada criança, com anotação em diário de campo das atividades, parceiros e cenários de compartilhamento do cuidado e da educação da criança. Os resultados apontam para: um intenso compartilhamento no grupo de vizinhança no acampamento e no grupo de família extensa no assentamento; a importância do cuidado e educação exercido entre as crianças, especialmente em situações de brincadeira; o histórico de migração como condição relacionada à maior busca pelo compartilhamento; a mulher como principal cuidadora, aspecto intimamente relacionado ao trabalho doméstico e na agricultura.O trabalho propicia reflexões acerca da diversidade dos modos de vida das crianças nestes contextos, sendo que há potencialidades educacionais ali construídas, fruto de uma riqueza cultural latente. Aponta ainda para considerações acerca das políticas públicas e garantia de direitos às crianças.

Saúde mental e os novos paradigmas de cidadania e inclusão social na sociedade contemporânea

Este estudo tem por objetivo analisar as categorias de cidadania e inclusão social na política de desinstitucionalização nos sujeitos em sofrimento psíquico diante do processo de individualização na teoria social contemporânea. Assume como hipótese que a saída do hospital psiquiátrico por si só não garante a inclusão social e nem o livre exercício da cidadania. Considerado o objetivo desta pesquisa, optou-se por fazer uma pesquisa bibliográfica como procedimento metodológico. O material de estudo foi dividido em três conjuntos: (1) 56 artigos científicos, visando a compreender a visão da academia; (2) um conjunto de legislação, composto de 10 leis que implementaram a política de desinstitucionalização no Brasil e a reforma dos serviços de saúde psiquiátrica, visando a compreender as ações do Estado; (3) quatro Relatórios Finais das quatro Conferências Nacionais de Saúde Mental, para também compreender a participação da sociedade civil. Para a análise do material, utilizou-se uma combinação de duas técnicas complementares: leitura bibliográfica com a análise de conteúdo. Dentre os vários processos que caracterizam a sociedade contemporânea, optou-se por analisar a individualização que impacta nas formas de exercício da cidadania e na inclusão social. Na análise dos resultados da categoria de cidadania foram identificadas associações em relação à interdição civil, liberdade, moradia, saúde, trabalho, educação e participação política. Relacionadas à categoria de inclusão social foram identificadas as referências à família, estigma, laços sociais, autonomia, contratualidade e trabalho. Os resultados obtidos indicam que o campo da saúde mental não está em completa consonância com as transformações da sociedade contemporânea, o que provoca um descolamento da realidade social da própria politica de desinstitucionalização e, portanto, maior dificuldade para a efetiva inclusão social e o exercício da cidadania desses indivíduos.

A individualização da medida cautelar pessoal no processo penal brasileiro

O sistema de medidas cautelares pessoais no processo penal brasileiro não mais gravita em torno da prisão preventiva, uma vez que o legislador instituiu um rol de medidas cautelares menos gravosas, a ela alternativas. Nesse contexto, como deve orientar-se a escolha judicial da medida a ser aplicada ao caso concreto? A constitucional idade de qualquer intervenção no direito fundamental de liberdade depende, essencialmente, de sua fundamentação constitucional, que é controlada a partir da proporcionalidade. A proporcional idade, portanto, é a pedra angular do sistema de medidas cautelares pessoais. A decisão que impõe uma medida cautelar pessoal jamais pode resultar de uma intuição individual misteriosa, senão de um procedimento cognoscitivo estruturado e comprovável de maneira intersubjetiva. Daí a importância da investigação da existência de um direito fundamental do imputado à individualização da medida cautelar pessoal, para afastar qualquer discricionariedade judicial na sua escolha. O objetivo do presente trabalho, portanto, é propor um método racional, baseado no exame da proporcionalidade, para controle intersubjetivo da justificação da decisão judicial que, no processo penal, imponha uma medida cautelar pessoal.