Fetal gene therapy: opportunities and risks

Advances in human prenatal medicine and molecular genetics have allowed the diagnosis of many genetic diseases early in gestation. In-utero transplantation of allogeneic hematopoietic stem cells (HSC) has been successfully used as a therapy in different animal models and recently also in human fetuses. Unfortunately, clinical success of this novel treatment is limited by the lack of donor cell engraftment in non-immunocompromised hosts and is thus restricted to diseases where the fetus is affected by severe immunodeficiency. Gene therapy using genetically modified autologous HSC circumvents allogeneic HLA barriers and constitutes one of the most promising new approaches to correct genetic deficits in the fetus. Recent developments of strategies to overcome failure of efficient transduction of quiescent hematopoietic cells include the use of new vector constructs and transduction protocols. These improvements open new perspectives for gene therapy in general and for prenatal gene transfer in particular. The fetus may be especially susceptible for successful gene therapy due to the immunologic naiveté of the immature hematopoietic system during gestation, precluding an immune reaction towards the transgene. Ethical issues, in particular those regarding treatment safety, must be taken into account before clinical trials with fetal gene therapy in human pregnancies can be initiated.

Controversies of fetal cardiac intervention

Remarkable advances in ultrasound imaging technology have made it possible to diagnose fetal cardiovascular lesions as early as 12-14 weeks of gestation and to assess their physiological relevance by echocardiography. Moreover, invasive techniques have been developed and refined to relieve significant congenital heart disease (CHD), such as critical aortic and pulmonary stenoses in the pediatric population including neonates. Recognition of the fact that certain CHDs can evolve in utero, and early intervention may improve the outcome by altering the natural history of such conditions has led to the evolution of a new fetal therapy, i.e. fetal cardiac intervention. Two entities, pulmonary valvar atresia and intact ventricular septum (PA/IVS) and hypoplastic left heart syndrome (HLHS), are associated with significant morbidity and mortality even with postnatal surgical therapy. These cases are believed to occur due to restricted blood flow, leading to impaired growth and function of the right or left ventricle. Therefore, several centers started the approach of antenatal intervention with the primary goal of improving the blood flow through the stenotic/atretic valve orifices to allow growth of cardiac structures. Even though centers with a reasonable number of cases seem to have improved the technique and the immediate outcome of fetal interventions, the field is challenged by ethical issues as the intervention puts both the mother and the fetus at risk. Moreover, the perceived benefits of prenatal treatment have to be weighed against steadily improving postnatal surgical and hybrid procedures, which have been shown to reduce morbidity and mortality for these complex heart defects. This review is an attempt to provide a balanced opinion and an update on fetal cardiac intervention.

Organotypic slice cultures from rat brain tissue: a new approach for Naegleria fowleri CNS infection in vitro

The free-living amoeba Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both, in vivo and in vitro models are currently being used to study PAM infection. However, animal models may pose ethical issues, are dependent upon availability of specific infrastructural facilities, and are time-consuming and costly. Conversely, cell cultures lack the complex organ-specific morphology found in vivo, and thus, findings obtained in vitro do not necessarily reflect the situation in vivo. The present study reports infection of organotypic slice cultures from rat brain with N. fowleri and compares the findings in this culture system with in vivo infection in a rat model of PAM, that proved complementary to that of mice. We found that brain morphology, as present in vivo, is well retained in organotypic slice cultures, and that infection time-course including tissue damage parallels the observations in vivo in the rat. Therefore, organotypic slice cultures from rat brain offer a new in vitro approach to study N. fowleri infection in the context of PAM.

INDUCED-PLURIPOTENT STEM-DERIVED NEURONAL PROGENITOR CELLS AS A NOVEL TREATMENT FOR NEURODEGENERATIVE DISEASES

Cellular therapies, as neuronal progenitor (NP) cells grafting, are promising therapies for patients affected with neurodegenerative diseases like Creutzfeldt-Jakob Disease (CJD). At this time there is no effective treatment or cure for CJD. The disease is inevitably fatal and affected people usually die within months of the appearance of the first clinical symptoms. Compelling evidence indicate that the hallmark event in the disease is the conversion of the normal prion protein (termed PrPC) into the disease-associated, misfolded form (called PrPSc). Thus, a reasonable therapeutic target would be to prevent PrP misfolding and prion replication. This strategy has been applied with poor results since at the time of clinical intervention substantial brain damage has been done. It seems that a more effective treatment aimed at patients with established symptoms of CJD would need to stop further brain degeneration or even recover some of the previously lost brain tissue. The most promising possibility to recover brain tissue is the use of NPs that have the potential to replenish the nerve cells lost during the early stages of the disease. Advanced cellular therapies, beside their potential for cell replacement, might be used as biomaterials for drug delivery in order to stimulate cell survival or the resolution the disease. Also, implanted cells can be genetically manipulated to correct abnormalities causing disease or to make them more resistant to the toxic microenvironments present in damaged tissue. In recent years cell engineering has been within the scope of the scientific and general community after the development of technologies able to “de-differentiate” somatic cells into induced-pluripotent stem (IPS) cells. This new tool permits the use of easy-to-reach cells like skin or blood cells as a primary material to obtain embryonic stem-like cells for cellular therapies, evading all ethical issues regarding the use of human embryos as a source of embryonic stem cells. The complete work proposes to implant IPS-derived NP cells into the brain of prion-infected animals to evaluate their therapeutic potential. Since it is well known that the expression of prion protein in the cell membrane is necessary for PrPSc mediated toxicity, we also want to determine if NPs lacking the prion protein have better survival rates once implanted into sick animals. The main objective of this work is to develop implantable neural precursor from IPS coming from animals lacking the prion protein. Specific aim 1: To develop and characterize cellular cultures of IPS cells from prp-/- mice. Fibroblasts from prp-/- animals will be reprogrammed using the four Yamanaka factors. IPS colonies will be selected and characterized by immunohistochemistry for markers of pluripotency. Their developmental capabilities will be evaluated by teratoma and embryoid body formation assays. Specific aim 2: To differentiate IPS cells to a neuronal lineage. IPS cells will be differentiated to a NP stage by the use of defined media culture conditions. NP cells will be characterized by their immunohistochemical profile as well as by their ability to differentiate into neuronal cells. Specific aim 3: Cellular labeling of neuronal progenitors cells for in vitro traceability. In order to track the cells once implanted in the host brain, they will be tagged with different methods such as lipophilic fluorescent tracers and transduction with GFP protein expression.

Da informação nossa de cada dia à Ciência da Informação : Conceitos, história, teorias e questões recentes

The work has as objective to produce a look about what we can think as a long history of information, what we think out from the most remote times until its conversion to theástatusáof object of the Information Science (IS) in the second half of 20th century. Of theorical nature and keeping up itself by the literature in IS and in similar areas, a discussion is made about the concept of information to then to list names, happenings and theories that contributed in the passage of the domain of the daily life to the domain of the Science. From a distant past to the most recent happenings connected to the problem of the privacity of the citizens in the digital networks, it is verified in the history of information a closed relation with the power, reason that suggests the deepening of the studies in IS about the political and ethical issues in the contemporary society.

La teoría emotivista de los valores de Bertrand Russell

Los asuntos éticos constituyeron una de las preocupaciones fundamentales de Bertrand Russell a lo largo de su vida. Luego de un pasar por un período caracterizado por una visión objetivista e intuicionista de los valores,Russell fue uno de los primeros en desarrollar una teoría emotivista de los valores. El objetivo de este artículo es presentar esta teoría a la vez que examinar los fundamentos en que se sostiene y mostrar sus implicancias.

Da informação nossa de cada dia à Ciência da Informação : Conceitos, história, teorias e questões recentes

The work has as objective to produce a look about what we can think as a long history of information, what we think out from the most remote times until its conversion to theástatusáof object of the Information Science (IS) in the second half of 20th century. Of theorical nature and keeping up itself by the literature in IS and in similar areas, a discussion is made about the concept of information to then to list names, happenings and theories that contributed in the passage of the domain of the daily life to the domain of the Science. From a distant past to the most recent happenings connected to the problem of the privacity of the citizens in the digital networks, it is verified in the history of information a closed relation with the power, reason that suggests the deepening of the studies in IS about the political and ethical issues in the contemporary society.

La teoría emotivista de los valores de Bertrand Russell

Los asuntos éticos constituyeron una de las preocupaciones fundamentales de Bertrand Russell a lo largo de su vida. Luego de un pasar por un período caracterizado por una visión objetivista e intuicionista de los valores,Russell fue uno de los primeros en desarrollar una teoría emotivista de los valores. El objetivo de este artículo es presentar esta teoría a la vez que examinar los fundamentos en que se sostiene y mostrar sus implicancias.

La teoría emotivista de los valores de Bertrand Russell

Los asuntos éticos constituyeron una de las preocupaciones fundamentales de Bertrand Russell a lo largo de su vida. Luego de un pasar por un período caracterizado por una visión objetivista e intuicionista de los valores,Russell fue uno de los primeros en desarrollar una teoría emotivista de los valores. El objetivo de este artículo es presentar esta teoría a la vez que examinar los fundamentos en que se sostiene y mostrar sus implicancias.

Da informação nossa de cada dia à Ciência da Informação : Conceitos, história, teorias e questões recentes

The work has as objective to produce a look about what we can think as a long history of information, what we think out from the most remote times until its conversion to theástatusáof object of the Information Science (IS) in the second half of 20th century. Of theorical nature and keeping up itself by the literature in IS and in similar areas, a discussion is made about the concept of information to then to list names, happenings and theories that contributed in the passage of the domain of the daily life to the domain of the Science. From a distant past to the most recent happenings connected to the problem of the privacity of the citizens in the digital networks, it is verified in the history of information a closed relation with the power, reason that suggests the deepening of the studies in IS about the political and ethical issues in the contemporary society.

La política editorial antifraude de las revistas científicas españolas e iberoamericanas del JCR en Ciencias Sociales

El proceso de publicación de un artículo debe basarse en la credibilidad, la verdad y la autenticidad. La inclusión de normas éticas en la política editorial científica se concibe como una medida preventiva y disuasoria de conductas inapropiadas. Dada la escasez de estudios sobre ética y publicación científica en Ciencias Sociales y, en particular, en España e Iberoamérica, esta investigación analiza la política editorial antifraude de las revistas españolas y latinoamericanas indexadas en el JCR en Ciencias Sociales (2014). Para cumplir nuestro objetivo, se utilizaron como muestra objeto de estudio 104 revistas y en las instrucciones a autores se examinaron una serie de principios de actuación ética: 1) Derechos de las personas que participan en la investigación; 2) Protección del bienestar de los animales objeto de experimentación; 3) Conflicto de interés; 4) Envío y publicación de manuscritos. Nuestros resultados apuntan que el carácter inédito de la investigación, así como la prohibición del envío simultáneo de los trabajos a otras revistas son los temas que aparecen con más frecuencia. Pese al intento de sociedades de edición científica como ICMJE y COPE por estandarizar los asuntos que afectan al fraude en la ciencia, su incidencia es exigua en las publicaciones objeto de estudio. Dada la dispersión normativa analizada, se retoma la necesidad detectada por otros autores de desarrollar un código ético uniforme para las disciplinas de Ciencias Sociales.

al- Nahj al-qawīm hadīyah li-man talaqqāhā bi-qalb salīm : manuscript, [ca. 1900]

The text starts with a praise of the Sultan Abdülhamid and his governor Osman Nuri Paşa. Then it discusses the necessity of obedience to the Sultan and the authorities from a religious point of view. It then touches briefly on several ethical issues. The text may or may not be complete at the end.

The future imagined: Exploring fiction as a means of reflecting on today’s Grand Societal Challenges and tomorrow’s options

European science policy (so-called Horizon 2020) is guided by Grand Societal Challenges (GSCs) with the explicit aim of shaping the future. In this paper we propose an innovative approach to the analysis and critique of Europe’s GSCs. The aim is to explore how speculative and creative fiction offer ways of embodying, telling, imagining, and symbolising ‘futures’, that can provide alternative frames and understandings to enrich the grand challenges of the 21st century, and the related rationale and agendas for ERA and H2020. We identify six ways in which filmic and literary representations can be considered creative foresight methods (i.e. through: creative input, detail, warning, reflection, critique, involvement) and can provide alternative perspectives on these central challenges, and warning signals for the science policy they inform. The inquiry involved the selection of 64 novels and movies engaging with notions of the future, produced over the last 150 years. Content analysis based on a standardised matrix of major themes and sub-domains, allows to build a hierarchy of themes and to identify major patterns of long-lasting concerns about humanity’s future. The study highlights how fiction sees oppression, inequality and a range of ethical issues linked to human and nature’s dignity as central to, and inseparable from innovation, technology and science. It concludes identifying warning signals in four major domains, arguing that these signals are compelling, and ought to be heard, not least because elements of such future have already escaped the imaginary world to make part of today’s experience. It identifies areas poorly defined or absent from Europe's science agenda, and argues for the need to increase research into human, social, political and cultural processes involved in techno-science endeavours.

How I Got Pregnant: Should Having a Child Justify a Partner’s ‘Deception’?

Réponse à - Travail créatif / Response to - Creative work

Guérir avec l'EMDR : preuves et controverses

L'EMDR est une thérapie qui a été développée pour traiter les souvenirs traumatiques, puis proposée pour traiter une variété de troubles psychologiques. Ce texte est le premier à recenser en français les études qui ont évalué l'efficacité de cette forme de thérapie. L'efficacité de l'EMDR est d'abord démontrée à l'aide d'études de cas qui comportent des limites importantes. Les études de cas basées sur un protocole expérimental donnent des résultats plus mitigés. Les études contrôlées qui examinent l'efficacité de l'EMDR sont ensuite décrites en fonction du type de contrôle exercé et du type de trouble traité. L'EMDR est aussi efficace que la thérapie cognitivocomportementale pour traiter le trouble de stress posttraumatique, mais pas pour le traitement de la phobie spécifique ni du trouble panique. De plus, les études montrent de façon répétée que l'absence des mouvements oculaires ne modifie pas l'efficacité de l'EMDR. Une analyse des différences et des similitudes entre l'EMDR et l'approche cognitivo-comportementale est présentée. Les caractéristiques pseudo-scientifiques qui ont marquées le développement et la diffusion de l'EMDR sont aussi abordées.