La gripe A desde la teoría de la elección racional: propuestas para la toma de decisiones de políticas preventivas

This article is a reflection on the social uncertainty caused by Influenza A and on the consequences that it can have on decision making in health promotion policies. We use concepts and metaphors of the Rational Choice Theory, among them, the “ingratitude effect” or the “distrust effect”, as we analyse how these can become obstacles for the efficiency of prevention policies. Then, we focus on the information asymmetry of the principal-agent relationship, and we propose measures to diminish the “moral risk” that they cause. We finish by advancing some proposals for designing lines and strategies of action in health promotion policies.

Present situation and new strategies for Chagas disease chemotherapy: a proposal

Treatments for Chagas disease have been administered since the first attempts by Mayer & Rocha Lima (1912, 1914) and up to the drugs currently in use (nifurtimox and benznidazole), along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles), in separate form. Several diseases such as tuberculosis, leprosy and AIDS only came under control after they were treated with associations of drugs with different mechanisms of action. This not only boosts the action of the different compounds, but also may avoid the development of parasite resistance .To this end, over the short term, we propose experimental studies on laboratory animals and clinical trials with the following associations: (i) nifurtimox (8 mg/kg/day) + benznidazole (5 mg/kg/day) x 60 consecutive days; (ii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + allopurinol (8-10 mg/kg/day) x 60 days and (iii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + ketoconazole, fluconazole or itraconazole (5-6 mg/kg/day) x 60 consecutive days. The doses of the drugs and the treatment schedules for the clinical trials must be adapted according to the side effects. From these, other double or triple associations could be made, using drugs with different mechanisms of action. This proposal does not exclude investigations on new drugs over the median and long terms, targeting other aspects of the metabolism of Trypanosoma cruzi. Until such time as the ideal drug for specific treatment of Chagas disease might be discovered, we need to develop new strategies for achieving greater efficacy with the old drugs in associations and to develop rational experimentation with new drugs.

Work Meaningfulness as a Key Enhancer of Ethical Values in Business

Despite abundant research on work meaningfulness, the link between work meaningfulness and general ethical attitude at work has not been discussed so far. In this article, we propose a theoretical framework to explain how work meaningfulness contributes to enhanced ethical behavior. We argue that by providing a way for individuals to relate work to one's personal core values and identity, work meaningfulness leads to affective commitment - the involvement of one's cognitive, emotional, and physical resources. This, in turn, leads to engagement and so facilitates the integration of one's personal values in the daily work routines, and so reduces the risk of unethical behavior. On the contrary, anomie, that is, the absence of meaning and consequently of personal involvement, will lead to lower rational commitment rather than affective commitment, and consequently to disengagement and a-morality. We conclude with implications for the management of ethical attitudes.

The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

Trypanosoma cruzi is a parasite that causes Chagas disease, which affects millions of individuals in endemic areas of Latin America. One hundred years after the discovery of Chagas disease, it is still considered a neglected illness because the available drugs are unsatisfactory. Aromatic compounds represent an important class of DNA minor groove-binding ligands that exhibit potent antimicrobial activity. This study focused on the in vitro activity of 10 aromatic dicationic compounds against bloodstream trypomastigotes and intracellular forms of T. cruzi. Our data demonstrated that these compounds display trypanocidal effects against both forms of the parasite and that seven out of the 10 compounds presented higher anti-parasitic activity against intracellular parasites compared with the bloodstream forms. Additional assays to determine the potential toxicity to mammalian cells showed that the majority of the dicationic compounds did not considerably decrease cellular viability. Fluorescent microscopy analysis demonstrated that although all compounds were localised to a greater extent within the kinetoplast than the nucleus, no correlation could be found between compound activity and kDNA accumulation. The present results stimulate further investigations of this class of compounds for the rational design of new chemotherapeutic agents for Chagas disease.

La maladie de Still de l'adulte [Adult-onset Still's disease]

La maladie de Still de l'adulte reste un diagnostic souvent évoqué, mais difficile à poser en l'absence d'anomalie clinique ou de laboratoire pathognomonique. Il est encore un diagnostic d'exclusion et la difficulté réside dans l'utilisation rationnelle et adéquate de ces tests d'exclusion. Le traitement reste quant à lui pragmatique, basé sur une analyse de situation et une définition claire des objectifs. Finalement, si les traitements biologiques semblent efficaces, ils restent réservés aux cas résistant aux traitements conventionnels ou corticodépendants. If the diagnosis of Adult-onset Still disease is often entertained, the disease remains difficult to diagnose in the absence of any specific clinical or laboratory anomaly. Diagnosis is still a diagnosis of exclusion, and the difficulty rests in the rational and appropriate use of those exclusion tests. Treatment is pragmatic, based on an analysis of the situation and a clear definition of the objectives. Finally, if biological treatments appear efficient, they should be reserved for patients resistant to conventional therapy or corticodependant

Identification of Schistosoma mansoni candidate antigens for diagnosis of schistosomiasis

The development of a more sensitive diagnostic test for schistosomiasis is needed to overcome the limitations of the use of stool examination in low endemic areas. Using parasite antigens in enzyme linked immunosorbent assay is a promising strategy, however a more rational selection of parasite antigens is necessary. In this study we performed in silico analysis of the Schistosoma mansoni genome, using SchistoDB database and bioinformatic tools for screening immunogenic antigens. Based on evidence of expression in all parasite life stage within the definitive host, extracellular or plasmatic membrane localization, low similarity to human and other helminthic proteins and presence of predicted B cell epitopes, six candidates were selected: a glycosylphosphatidylinositol-anchored 200 kDa protein, two putative cytochrome oxidase subunits, two expressed proteins and one hypothetical protein. The recognition in unidimensional and bidimensional Western blot of protein with similar molecular weight and isoelectric point to the selected antigens by sera from S. mansoni infected mice indicate a good correlation between these two approaches in selecting immunogenic proteins.

Laboratory detection of respiratory viruses by automated techniques.

Advances in clinical virology for detecting respiratory viruses have been focused on nucleic acids amplification techniques, which have converted in the reference method for the diagnosis of acute respiratory infections of viral aetiology. Improvements of current commercial molecular assays to reduce hands-on-time rely on two strategies, a stepwise automation (semi-automation) and the complete automation of the whole procedure. Contributions to the former strategy have been the use of automated nucleic acids extractors, multiplex PCR, real-time PCR and/or DNA arrays for detection of amplicons. Commercial fully-automated molecular systems are now available for the detection of respiratory viruses. Some of them could convert in point-of-care methods substituting antigen tests for detection of respiratory syncytial virus and influenza A and B viruses. This article describes laboratory methods for detection of respiratory viruses. A cost-effective and rational diagnostic algorithm is proposed, considering technical aspects of the available assays, infrastructure possibilities of each laboratory and clinic-epidemiologic factors of the infection.

Graph based study of allergen cross-reactivity of plant lipid transfer proteins (LTPs) using microarray in a multicenter study.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens.

Perioperative intravenous iron; an upfront therapy for treating anaemia and reducing transfusion requirements.

Perioperative anaemia, with iron deficiency being its leading cause, is a frequent condition among surgical patients, and has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Postoperative anaemia is even more frequent and is mainly caused by perioperative blood loss, aggravated by inflammation-induced blunting of erythropoiesis. Allogenic transfusion is commonly used for treating acute perioperative anaemia, but it also increases the rate of morbidity and mortality in surgical and critically ill patients. Thus, overall concerns about adverse effects of both preoperative anaemia and allogeneic transfusion have prompted the review of transfusion practice and the search for safer and more biologically rational treatment options. In this paper, the role of intravenous iron therapy (mostly with iron sucrose and ferric carboxymaltose), as a safe and efficacious tool for treating anaemia and reducing transfusion requirements in surgical patients, as well as in other medical areas, has been reviewed. From the analysis of published data and despite the lack of high quality evidence in some areas, it seems fair to conclude that perioperative intravenous iron administration, with or without erythropoiesis stimulating agents, is safe, results in lower transfusion requirements and hastens recovery from postoperative anaemia. In addition, some studies have reported decreased rates of postoperative infection and mortality, and shorter length of hospital stay in surgical patients receiving intravenous iron.

Prescripción enfermera en el entorno de las urgencias y emergencias. Marco conceptual vs entorno legislado en España

The prescription, widely discussed and defined conceptually in recent years in an environment of widening the spectrum of responsibilities nurse, has capacity for integration and definition in the area of accident and emergency care and carried out over the patient urgently, about emergencies and life-long commitment. Be necessary to frame throughout the legal framework, following the amendment of the Twelfth Additional Provision of Law 29/2006 of guarantees and rational use of drugs and medical devices, can be waived and implementation required, provided under model and through the nursing process and method and as an exponent and endorsementn of science and advanced clinical practice, to join the idea of interdisciplinary professional consensus that the law posed by the preparation and implementation of standardized protocols, algorithms and / or clinical practice guidelines in the context of what has come to be called "collaborative standard prescription": Prescription to the nurse in certain clinical situations in terms of a performance protocol, agreed with multidisciplinary team care health of the population (Group Protocols), which can be considered an intermediate step in the evolution towards independent nurse prescribing, providing nurses experience of a prescription under these protocols and demonstrating their capabilities.

Switch-peptides: From conformational studies to Alzheimer's disease

Studies on designed peptides that exhibit high tendencies for medium-induced conformational transitions have recently attracted much attention because structural changes are considered as molecular key processes in degenerative diseases. The experimental access to these events has been limited so far mainly due to the intrinsic tendency of the involved polypeptides for self-association and aggregation, e.g. amyloid P plaque formation, thought to be at the origin of Alzheimer's disease. We have developed a new concept termed 'switch-peptides' which allows the controlled onset of polypeptide folding and misfolding in vitro and in vivo, starting from a soluble, non-toxic precursor molecule. As a major feature, the folding process is initiated by enzyme-triggered N,O-acyl migrations restoring the native peptide backbone in situ. As the folding is set off in the moment of creating the bioactive molecule ('in statu nascendi', ISN), our concept allows for the first time the investigation of the early steps of protein misfolding as relevant in degenerative diseases, opening new perspectives for the rational design of therapeutically relevant compounds.

La protecció de la part feble del contracte en el dret civil català i en el dret civil europeu

La investigación analiza si, con el horizonte del Libro Sexto del Código Civil de Cataluña relativo a las obligaciones y los contratos, el legislador catalán tiene que mantener el modelo tradicional de la rescisión por lesión ultradimidium, o bien tiene que integrar esta institución en el marco de la protección de la parte débil del contrato, en la línea de las modernas propuestas de derecho europeo.

RNA interference screening identifies a novel role for autocrine fibroblast growth factor signaling in neuroblastoma chemoresistance.

Chemotherapeutic drug resistance is one of the major causes for treatment failure in high-risk neuroblastoma (NB), the most common extra cranial solid tumor in children. Poor prognosis is typically associated with MYCN amplification. Here, we utilized a loss-of-function kinome-wide RNA interference screen to identify genes that cause cisplatin sensitization. We identified fibroblast growth factor receptor 2 (FGFR2) as an important determinant of cisplatin resistance. Pharmacological inhibition of FGFR2 confirmed the importance of this kinase in NB chemoresistance. Silencing of FGFR2 sensitized NB cells to cisplatin-induced apoptosis, which was regulated by the downregulation of the anti-apoptotic proteins BCL2 and BCLXL. Mechanistically, FGFR2 was shown to activate protein kinase C-δ to induce BCL2 expression. FGFR2, as well as the ligand fibroblast growth factor-2, were consistently expressed in primary NB and NB cell lines, indicating the presence of an autocrine loop. Expression analysis revealed that FGFR2 correlates with MYCN amplification and with advanced stage disease, demonstrating the clinical relevance of FGFR2 in NB. These findings suggest a novel role for FGFR2 in chemoresistance and provide a rational to combine pharmacological inhibitors against FGFR2 with chemotherapeutic agents for the treatment of NB.

New insights to occult gastrointestinal bleeding: From pathophysiology to therapeutics.

Obscure gastrointestinal bleeding is still a clinical challenge for gastroenterologists. The recent development of novel technologies for the diagnosis and treatment of different bleeding causes has allowed a better management of patients, but it also determines the need of a deeper comprehension of pathophysiology and the analysis of local expertise in order to develop a rational management algorithm. Obscure gastrointestinal bleeding can be divided in occult, when a positive occult blood fecal test is the main manifestation, and overt, when external sings of bleeding are visible. In this paper we are going to focus on overt gastrointestinal bleeding, describing the physiopathology of the most usual causes, analyzing the diagnostic procedures available, from the most classical to the novel ones, and establishing a standard algorithm which can be adapted depending on the local expertise or availability. Finally, we will review the main therapeutic options for this complex and not so uncommon clinical problem.