Evolución del virus de la inmunodeficiencia humana tipo 1 en pacientes no progresores virémicos

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 14-01-2020El objetivo principal de este trabajo fue el estudio del virus de la Inmunodeficiencia Humana Tipo 1 (VIH-1) en un grupo de pacientes no progresores a largo plazo (LTNP), virémicos, concretamente en un subgrupo que denominamos como modernos. Basándonos en el análisis de las secuencias nucleotídicas de la región C2-V5 del gen env de diferentes aislados en distintas zonas geográficas de España, establecimos una correlación entre la distancia genética de estas y la fecha de recogida de la muestra, lo cual nos permitía estimar la datación de las secuencias genéticas. Con este estudio, fuimos capaces de determinar la existencia de dos grupos de individuos dentro del grupo de LTNP. Definimos un primer grupo de individuos LTNP “ancestrales”, los cuales se caracterizaban por presentar secuencias nucleotídicas ancestrales cercanas a la fecha de seroconversión del individuo; y un segundo grupo de LTNP, que denominamos “modernos”, que tenían secuencias cercanas a la fecha de extracción de la muestra. La evolución viral se analizó utilizando el ADN extraído de células mononucleares de sangre periférica (CMSP) de ocho LTNP “modernos” con más de diez años de infección en ausencia de tratamiento antirretroviral. Los árboles filogenéticos de máxima verosimilitud (ML) mostraron dos patrones de evolución claramente diferenciados; uno caracterizado por presentar árboles filogenéticos similares a los que se encuentran en individuos con progresión crónica (PC), en los que hay un reemplazamiento de los linajes virales en el tiempo (evolución “temporal”). El segundo patrón evolutivo encontrado se caracterizaba por la pérdida de estructura temporal anteriormente descrita, es decir, las variantes virales que están circulando en un momento dado no son el origen de las variantes detectadas en momentos inmediatamente posteriores, y se distribuyen aleatoriamente a lo largo de todo árbol. Con este análisis encontramos que uno de los individuos LTNP “moderno” estaba doblemente infectado manteniendo su estatus de LTNP durante casi treinta años. Realizamos un análisis de las características clínicas, virológicas e inmunológicas de los individuos LTNP modernos con el objetivo de determinar la influencia de estos patrones de evolución viral distintos en el curso clínico de la enfermedad, concluyendo que los individuos con un patrón de evolución “atemporal” parecen tener un mejor pronóstico de la enfermedad. Por último, estudiamos la pérdida de control de la enfermedad en dos de los pacientes LTNP “modernos”. Analizamos los factores virológicos responsables de dicha pérdida del estatus LTNP y encontramos cambios en las subpoblaciones virales asociados a un aumento en la capacidad replicativa de los virus que produjeron cambios en la progresión de la enfermedad.The main goal of the project was to study the evolution of the human immunodeficiency virus type 1 (HIV-1) in a group of long-term non-progressor patients (LTNP), particularly in a sub-group classified as modern. Based on the analysis of the nucleotide sequence in C2-V5 region of env gene of the viruses from different isolates collected in different geographical areas of Spain, we established a correlation between the genetic distance and the date of the specimen collection. Based on this thechnique, we were able to determine the existence of two groups within LTNP. We defined a group of “ancestral” LTNP who showed only ancestral nucleotide sequences close in the dating to the time of seroconversion; and a second group of LTNP, referred to as “modern” subjects, displaying modern viral dating, with the estimation time of the sequence close to the sampling date. Viral evolution was analyzed using the viral DNA extracted from the PBMCs of eight HIV-1 modern LTNP with more than ten years of infection and who remain healthy in absence of antiretroviral therapy The Maximum likelihood (ML) phylogenetic trees showed in env gene sequences two different evolutionary patterns; one displayed a strong temporal structure similar to the pattern described in chronicles progressors, characterized by the continual replacement of viral variants with time (temporal evolution). The second evolutionary pattern found was characterized by the lack of temporal structure previously describe, meaning, viral variants present in one sample were not the origin of the viral variants detected immediately after, and were ramdonly distributed on the phylogenetic tree. Based on this study, we were able to determine the existence of one dual infected LTNP modern patient. We carried out a clinical, virological and inmunological analysis of “modern” LTNP to determine if different evolutionay pattern found were affecting the disease progression, concluding that subjects with “atemporal” evolutionary viral pattern seem to have better disease prognosis. Finally, we studied the loss viral control in two of this LTNP subjects. We analized the role of viral factors in this loss finding that switch of HIV-1 subpopulation associated with enhanced viral replication capacity results in changes in the disease progression

Centro Cochrane do Brasil: 15º aniversário

Universidade Federal de São Paulo (UNIFESP) Program on Internal Medicine and TherapeuticsBrazilian Cochrane CenterDivision of Emergency and Evidence-Based MedicineUNIFESP, Program on Internal Medicine and TherapeuticsSciEL

Eficácia e segurança dos antipsicóticos atípicos (quetiapina, risperidona, aripiprazol, paliperidona) em comparação com um placebo ou medicamentos antipsicóticos típicos no tratamento da esquizofrenia refratária: overview de revisão sistemática

CONTEXT AND OBJECTIVE: According to some cohort studies, the prevalence of refractory schizophrenia (RS) is 20-40%. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS. METHODS: This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs) on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline) (1966-2009), Controlled Trials of the Cochrane Collaboration (2009, Issue 2), Embase (Excerpta Medica) (1980-2009), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) (1982-2009). There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included. RESULTS: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine. CONCLUSIONS: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.CONTEXTO E OBJETIVO: De acordo com alguns estudos de coorte, a prevalência da esquizofrenia refratária (ER) está entre 20-40%. Nosso objetivo foi avaliar a efetividade e segurança de aripiprazol, paliperidona, quetiapina e risperidona no tratamento da esquizofrenia refratária. MÉTODOS: Avaliação crítica das revisões Cochrane publicadas na Biblioteca Cochrane e complementação com referências de ensaios clínicos randomizados (ECRs) mais atualizados sobre ER. As seguintes bases de dados foram pesquisadas: Medline (Medical Literature Analysis and Retrieval System Online) (1966-2009), Ensaios Controlados da Colaboração Cochrane (2009, edição 2), Embase (Excerpta Database) (1980-2009), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) (1982-2009). Não houve restrição a idiomas. Ensaios clínicos randomizados, revisões sistemáticas e metanálises que avaliaram antipsicóticos atípicos no tratamento da esquizofrenia refratária foram incluídos. RESULTADOS: Sete revisões sistemáticas Cochrane e 10 ECRs complementares foram incluídos nessa revisão. No geral os dados demonstram pequenas diferenças entre os antipsicóticos atípicos avaliados e os típicos na melhora dos sintomas da doença, apesar da melhor adesão ao tratamento com os atípicos. A risperidona foi avaliada especificamente em pacientes com esquizofrenia refratária em uma das revisões sistemáticas incluídas, a qual demonstrou desfechos favoráveis, porém não definitivos quando comparada a drogas também com eficácia comprovada como amisulprida, clozapina e olanzapina. CONCLUSÕES: Os dados reforçam a dificuldade de tratar esses pacientes, com elevadas taxas de desistência do tratamento e padrões de melhora modestos nas avaliações de eficácia. Os antipsicóticos atípicos têm vantagens sobre os típicos principalmente pelo melhor perfil de segurança, o que leva a melhor adesão ao tratamento. A associação de antipsicóticos também pode ser uma opção em alguns pacientes refratários ao tratamento.Universidade Federal de São Paulo (UNIFESP) Brazilian Cochrane CenterUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Brazilian Cochrane CenterUNIFESP, Brazilian Cochrane CenterUNIFESP, EPM, Brazilian Cochrane CenterSciEL

Long-term photosynthetic CO2 removal from biogas and flue-gas: Exploring the potential of closed photobioreactors for high-value biomass production

Producción CientíficaThe long-term performance of a tubular photobioreactor interconnected to a gas absorption column for the abatement of CO2 from biogas and flue-gas was investigated. Additionally, a novel nitrogen feast-famine regime was implemented during the flue-gas feeding stage in order to promote the continuous storage of highly-energetic compounds. Results showed effective CO2 (~98%) and H2S (~99%) removals from synthetic biogas, supported by the high photosynthetic activity of microalgae which resulted in an alkaline pH (~10). In addition, CO2 removals of 99 and 91% were observed during the flue-gas operation depending on the nutrients source: mineral salt medium and digestate, respectively. A biomass productivity of ~8 g m−2 d−1 was obtained during both stages, with a complete nitrogen and carbon recovery from the cultivation broth. Moreover, the strategy of feeding nutrients during the dark period promoted the continuous accumulation of carbohydrates, their concentration increasing from 22% under normal nutrition up to 37% during the feast-famine cycle. This represents a productivity of ~3 g-carbohydrates m−2 d−1, which can be further valorized to contribute to the economic sustainability of the photosynthetic CO2 removal process.2019-12-312019-12-31Ministerio de Economía, Industria y Competitividad (Project CTM2015-70722-R

When Virtual Assistants Meet Teledermatology: Validation of a Virtual Assistant to Improve the Quality of Life of Psoriatic Patients

Teledermatology has given dermatologists a tool to track patients’ responses to therapy using images. Virtual assistants, the programs that interact with users through text or voice messages, could be used in teledermatology to enhance the interaction of the tool with the patients and healthcare professionals and the overall impact of the medication and quality of life of patients. As such, this work aimed to investigate the effectiveness of using a virtual assistant for teledermatology and its impact on the quality of life. We conducted surveys with the participants and measured the usability of the system with the System Usability Scale (SUS). A total of 34 participants (30 patients diagnosed with moderate-severe psoriasis and 4 healthcare professionals) were included in the study. The measurement of the improvement of quality of life was done by analyzing Psoriasis Quality of Life (PSOLIFE) and Dermatology Life Quality Index (DLQI) questionnaires. The results showed that, on average, the quality of life improved (from 63.8 to 64.8 for PSOLIFE (with a p-value of 0.66 and an effect size of 0.06) and 4.4 to 2.8 for DLQI (with a p-value of 0.04 and an effect size of 0.31)). Patients also used the virtual assistant to do 52 medical consultations. Moreover, the usability is above average, with a SUS score of 70.1. As supported by MMAS-8 results, adherence also improved slightly. Our work demonstrates the improvement of the quality of life with the use of a virtual assistant in teledermatology, which could be attributed to the sense of security or peace of mind the patients get as they can contact their dermatologists directly within the virtual assistant-integrated system

Macroinvertebrate biomass estimates in Cantabrian streams and relationship with brown trout (Salmo trutta) populations

In this work, the average biomass of 80 relatively common families of benthic macroinvertebrates in the streams of the Biscay region (Basque Country, northern Iberian Peninsula) was estimated. The macroinvertebrates were collected using a kick net and preserved alive in cool aerated stream water. The fresh weight, dry weight, and ash-free dry weight (AFDW) were obtained for each family. The biomass values obtained were applied to more than a hundred macroinvertebrate samples collected from 1997 to 2006 in 17 stretches of 14 rivers inhabited by brown trout. The total and partial biomass of each sample was estimated. Significant differences in the density (F = 2.91; df = 16, 100; P < 0.001) and biomass (F = 6.52; df = 16, 100; P < 0.001) of the macroinvertebrates occurred among the stations, with up to a 11-fold and 17-fold range, respectively. The brown trout population size was positively correlated to both the macroinvertebrate abundance and biomass. By age classes, this relationship was significant for only the 1+ and 2+ trout. The AFDW metric is recommended because it represents the real organic biomass value that joins the trophic food chain, avoiding an overestimation of the energy contribution of taxa with shells or cases. The Gammaridae had higher values of AFDW than expected, due to their high content of organic matter. A positive selection of gammarids by the trout was also observed in some cases.Se ha estimado la biomasa media de las 80 familias de macroinvertebrados bentónicos presentes habitualmente en ríos de Bizkaia (País Vasco, Norte de la Península Ibérica). Los macroinvertebrados se recogieron con red Kick y se conservaron vivos en agua del río con aireación forzada. Se obtuvo el peso fresco, el peso seco y el peso seco libre de cenizas (PSLC) para cada familia. Estos valores de biomasa se aplicaron a más de un centenar de muestras de macroinvertebrados recogidas entre 1997 y 2006 en 17 tramos de 14 ríos habitados por trucha común. Se estimó la biomasa total y parcial para cada muestra. Se observaron diferencias significativas entre las estaciones, de hasta 11 veces en términos de abundancia (F = 2.91; df = 16, 100; P < 0.001) y de hasta 17 veces en la biomasa total (F = 6.52; df = 16, 100; P < 0.001) de macroinvertebrados. El tamaño de la población de truchas apareció correlacionado positivamente con la abundancia y biomasa total de macroinvertebrados. Diferenciando por clases de edad, estas relaciones fueron significativas sólo para las clases 1+ y 2+. Se recomienda el uso del PSLC ya que éste representa la fracción de biomasa que realmente se incorpora a la cadena trófica, evitando sobrevalorar la aportación energética de los taxones con conchas o estuches. Los gammáridos mostraron valores de PSLC mayores de los esperados, lo que conlleva un elevado contenido en materia orgánica. En algunos casos, la trucha seleccionaba positivamente este grupo

The Socio-educational, Psychological and Family-Related Antecedents of Entrepreneurial Intentions among Spanish Youth

Despite the abundant scientific literature on entrepreneurship, there is still only limited information on young students’ entrepreneurial intentions. The reasons for this, may be generally found in the different conceptual approaches to entrepreneurial intention, and particularly in the variables that regulate and act as antecedents to such intentions. This bias has generated different lines of investigation into the factors relating to entrepreneurial intention among students. One line of investigation is centered on the variables that influence entrepreneurial intention, in particular, relational, educational, and psychological variables, and another is centered on the antecedents of entrepreneurial intention, amongst which is entrepreneurial interest. In this paper, we seek to analyze the relationship between the entrepreneurial interest of Spanish youth and a set of socio-educational, psychological, and health-related variables using principal component analysis. A previously validated ad hoc questionnaire was administered to 1764 students (15–18 years old). Notably, few Spanish youth expressed significantly high entrepreneurial interest; those who did were mostly men with a family tradition of entrepreneurial parents, who held high perceptions of their health and quality of life, and considered it important in business to detect opportunities beforehand and to create employment. Their principal motives were to improve their professional development, to put their ideas into practice, and to achieve economic independence. This paper proposes the early detection of entrepreneurial interests in young people in order to reinforce these interests as potential long-term initiatives.This research was funded by MINISTRY OF ECONOMY AND COMPETITIVENESS. GOVERNMENT OF SPAIN, grant number EDU 2012-39080-C07-00 a 07

Entrepreneurial Interest and Entrepreneurial Competence Among Spanish Youth: An Analysis with Artificial Neural Networks

Studies of the socio-economic function of entrepreneurship have emphasized the critical role that entrepreneurial competence and its implementation play at different stages of the education system. In this paper, as a research objective, we seek to determine the entrepreneurial interest of Spanish youth aged between 15 and 18 years of age enrolled in formal secondary education programs, an initial stage in the development of entrepreneurship. A previously validated ad hoc questionnaire is applied through simple random sampling to 1764 students at secondary school in Spain. A descriptive cross-sectional study is carried out. The analysis is done with Artificial Neural Networks (ANNs), a technique that reduces the high dimensionality of data through Cooperative Maximum Likelihood Hebbian Learning (CMLHL), applying neurocomputational methods to the educational sciences. We find as key results that Spanish youth express a medium level of interest in entrepreneurship. Analysis with ANNs shows that education in entrepreneurial competence is an influential aspect of interest in entrepreneurship. As a conclusion, our results suggest that educational and curricular reforms must be undertaken to promote the development of entrepreneurial competence at various stages of education in order to increase interest in entrepreneurship.This research was funded by MINISTRY OF ECONOMY AND COMPETITIVENESS. GOVERNMENT OF SPAIN, grant number EDU 2012-39080-C07-00 a 07