Health technology assessment in evolution - focal therapy in localised prostate cancer.

Focal therapy in prostate cancer aims to treat only the part of the gland harboring clinically significant disease while preserving the rest of the tissue. This approach may substantially reduce treatment-related toxicity without compromising disease control outcomes. Short- to medium-term functional and oncological results in prospective interventional studies are promising, but comparative effectiveness research against standard of care is required to incorporate focal therapy among standard options. In this review, we discuss the actual stage of assessment and results of sources of energy commonly used to deliver focal therapy. We also provide our viewpoint on how the field will evolve in the near future.

Mobilizing and evaluating anticancer T cells: pitfalls and solutions.

Immunotherapy is a promising means to fight cancer, prompting a steady increase in clinical trials and correlative laboratory studies in this field. As antitumor T cells play central roles in immunity against malignant diseases, most immunotherapeutic protocols aim to induce and/or strengthen their function. Various treatment strategies have elicited encouraging clinical responses; however, major challenges have been uncovered that should be addressed in order to fully exploit the potential of immunotherapy. Here, we outline pitfalls for the mobilization of antitumor T cells and offer solutions to improve their therapeutic efficacy. We provide a critical perspective on the main methodologies used to characterize T-cell responses to cancer therapies, with a focus on discrepancies between T-cell attributes measured in vitro and protective responses in vivo. This review altogether provides recommendations to optimize the design of future clinical trials and highlights important considerations for the proficient analysis of clinical specimens available for research.

El poder de las imágenes en los "Diálogos de Medallas, inscriciones y otras antigüedades" (1587) de don Antonio Agustín

Un aspecto realmente sorprendente y fascinante, el cual hasta ahora no se ha prestado demasiada atención, es el poder de las imágenes en el famosísimo y reputado libro de Don Antonio Agustín, los Dialogos de Medallas, publicado en Tarragona por Felipe Mey en el año 15872. Las imágenes que ilustran este libro fueron las responsables de una serie de fenómenos de gran importancia en la génesis de esta edición. El primero de ellos fue la dilatada espera de la edición a causa de la recepción de los grabados. El segundo hace referencia a la misma ordenación de las imágenes, ya que mientras muchos libros de numismática las organizan atendiendo a sucronología, a sus medidas o al material en el que están labradas, las imágenes del libro de Agustín se organizan teniendo en cuenta el texto, hecho que provoca que estos iconos tengan un fuerte carácter didascálico. En tercer lugar, hay que resaltar la pertinaz voluntad y los probados esfuerzos de Agustín para conseguir unas imágenes de calidad en Roma, puesto que los talleres gráficos españoles dejaban mucho que desear en esta época. Y por último, cabe subrayar que su muerte en Tarragona en mayo de 1586, interrumpió el proceso del grabado de las monedas, hecho que motivo que solamente estuvieran ilustrados los dos primeros diálogos de su libro. Pero antes de entrar en la valoración de estos fenómenos veamos unos breves prologomenos.

Allergen-specific immunotherapy of allergy and asthma: current and future trends.

Allergen-specific immunotherapy is the only immunomodulatory and etiological therapy of allergy and asthma. Conventional specific immunotherapy (SIT) with whole-allergen extract is antigen specific, effective on multiple organs, efficient on asthma in defined conditions, provides long-lasting protection and is cost effective. Moreover, SIT is able to prevent the course of rhinitis to asthma. SIT has its drawbacks: the long duration of treatment, the unsatisfactory standardization of allergen extracts and a questionable safety level. Novel approaches are aimed at drastically reducing adverse anaphylactic events, shortening the duration of therapy and improving its efficacy. Novel promising approaches have based their formulation on a limited set of recombinant allergens or chimeric molecules as well as on hypoallergenic allergen fragments or peptides. The simultaneous use of adjuvants with immunomodulatory properties may contribute to improve both the safety and efficacy of allergen-SIT of allergy and asthma.

Influence of CD4+/CD25+ regulatory T cells on atherogenesis in patients with end-stage kidney disease.

Atherosclerosis, which is influenced by both traditional and nontraditional cardiovascular risk factors and has been characterized as an inflammatory process, is considered to be the main cause of the elevated cardiovascular risk associated with chronic kidney disease. The inflammatory component of atherosclerosis can be separated into an innate immune response involving monocytes and macrophages that respond to the excessive uptake of lipoproteins and an adaptive immune response that involves antigen-specific T cells. Concurrent with the influx of immune cells to the site of atherosclerotic lesion, the role of the adaptive immune response gradually increases. One of those cells are represented by the CD4+/CD25+ Tregs, which play indispensable roles in the maintenance of natural self-tolerance and negative control of pathological, as well as physiological, immune responses. Altered self-antigens such as oxidized LDLs may induce the development of CD4+/CD25+ Tregs with atheroprotective properties. However, atherosclerosis may be promoted by an imbalance between regulatory and pathogenic immunity that may be represented by the low expression of the forkhead box transcription factor (Foxp3) in CD4+/CD25+ Tregs. Such a defect may break immunologic tolerance and alter both specific and bystander immune suppression, leading to exacerbation of plaque development. Patients with end-stage kidney disease (ESKD) display a cellular immune dysfunction and accelerated atherosclerosis. Uremic solutes that accumulate during ESKD may be involved in these processes. In patients with ESKD and especially in those that are chronically hemodialyzed, oxidative stress induced by oxidized LDLs may increase CD4+/CD25+ Treg sensitivity to Fas-mediated apoptosis as a consequence of specific dysregulation of IL-2 expression. This review will focus on the current state of knowledge regarding the influence of CD4+/CD25+ Tregs on atherogenesis in patients with ESKD, and the potential effect of statins on the circulating number and the functional properties of these cells.

War and the evolution of belligerence and bravery.

Tribal war occurs when a coalition of individuals use force to seize reproduction-enhancing resources, and it may have affected human evolution. Here, we develop a population-genetic model for the coevolution of costly male belligerence and bravery when war occurs between groups of individuals in a spatially subdivided population. Belligerence is assumed to increase an actor's group probability of trying to conquer another group. An actor's bravery is assumed to increase his group's ability to conquer an attacked group. We show that the selective pressure on these two traits can be substantial even in groups of large size, and that they may be driven by two independent reproduction-enhancing resources: additional mates for males and additional territory (or material resources) for females. This has consequences for our understanding of the evolution of intertribal interactions, as hunter-gatherer societies are well known to have frequently raided neighbouring groups from whom they appropriated territory, goods and women.

Anciens catalogues de la Bibliothèque du Roi et de différentes collections qui sont venues l'accroître aux XVIIe, XVIIIe et XIXe siècles. Catalogues de divers fonds orientaux.

« Notices sur quelques manuscrits arabes, par M. Woepke (fol. 1) ; — Notices sur quelques mss. sanscrits, par M. Fauriel (fol. 6) ; — Notices sur quelques mss. sanscrits (fol. 40) ; — Notices sur quelques mss. sanscrits en caractère bengali, par M. Loiseleur Deslongchamps (fol. 58) ; — Notices sur quelques mss. arabes, par M. Hassler (fol. 94) ; — Notices sur quelques mss. arabes, par M. Reinaud (fol. 99) ; — Catalogue des mss. orientaux de l'ancienne maison de la Sorbonne, par M. Reinaud (fol. 126) ; — Catalogue des mss. orientaux de l'ancien couvent de l'Oratoire, par M. Reinaud (fol. 136) ; — Catalogue des mss. orientaux des différentes bibliothèques publiques de Paris (fol. 146) ; — Liste des livres et des mss. orientaux venus d'Alger et adressés à la Bibliothèque royale, le 30 nov. 1832 (fol. 152) ; — Note de quelques mss. orientaux appartenant à M. Wahl (fol. 156) ; — Mss. orientaux provenant de feu M. Schultz (fol. 157 et 159) ; — Mss., papiers et autres objets provenant de feu M. Schultz (fol. 163) ; — Collection Asselin (fol. 165 et 270) ; — Lettres et pièces relatives au fonds Asselin (fol. 263) ; — Mss. arabes, persans, samskrits et hindous tanys, cédés à la Bibliothèque du Roi par M. de Polier (fol. 291 et 293) ; — Évaluation de 47 mss. arabes, persans, maures, bengalis, etc., provenant de feu Ouessant, interprète de la Compagnie de Pondichéry (fol. 295) ; — Mss. arabes, turcs et persans de M. Ducaurroy (fol. 298) ; — Collection des mss. orientaux appartenant à la succession de feu M. le baron Rousseau, consul général à Tripoly de Barbarie (fol. 303) ; — Liste des mss. tamouls cédés à la Bibliothèque du Roi par M. Ducler (fol. 309) ; — Liste des mss. tamouls donnés à la Bibliothèque du Roi par M. Reydelet (fol. 311) ; — Mss, arabes et berbères de M. Delaporte père, 4848 (fol. 314) ; — État sommaire de quelques mss. réputés venir de feu M. Huet,... trouvés dans la maison Kerboeuf (fol. 323) ; — Mss. orientaux distraits du fonds Renaudot (fol. 324) ; — Mss. arabes rapportés d'Égypte par le citoyen Raiye (fol. 325) ; — Cinq volumes arabes mss. offerts à la Bibliothèque royale par S. A. R. Mgr le duc de Nemours (fol. 326) ; — Liste des livres qu'on a envoyés à Mrs de la Compagnie, en tamoul, 14 déc. 1729 (fol. 327) ; — Catalogue des mss. indiens de la Bibliothèque du Roi (fol. 328) ; — « Mémoire concernant l'acquisition des mss. persiens qu'il conviendroit de faire aux Indes pour la Bibliothèque du Roy » (fol. 362) ; — Mémoire de livres à rechercher dans le Levant pour la Bibliothèque du Roy (fol. 366) ; — État des mss. à rechercher à Constantinople pour la Bibliothèque impériale (fol. 384) ; — Catalogue des mss. orientaux appartenant à M. R. Johnson, 1806 (fol. 386) ; — Liste des mss. orientaux de la bibliothèque de sir Thomas Phillipps à Middlehill, 1829 (fol. 396) ; — Indication des mss. arabes les plus importants de la bibliothèque d'Alger (fol. 398) ; — Liste des livres et mss. venus d'Alger (fol. 402) ; — Liste des bibliothèques turques de Constantinople, 1854 (fol. 404) ; — Bibliothèque du sultan Ahmet III, au vieux sérail : catalogue des livres d'histoire, 1854 (fol. 408) ; — Note des mss. orientaux extraits de la bibliothèque de Vienne, que le conservatoire de la Bibliothèque impériale juge entièrement inutiles (fol. 416) ; — Notice par Ascari de l'ancien ms. syriaque 13 (fol. 418) ; — Manuscrits persans historiques de l'Indoustan, et livres en langue samscretam, apportés à la Bibliothèque du Roi en 1778 » (fol. 420).

QuantiFERON-TB Gold assay for the diagnosis of latent tuberculosis infection.

Tuberculin skin test (TST) has been used for 100 years for the diagnosis of latent tuberculosis (TB) infection (LTBI). In recent years, increasing interest in the diagnosis of TB has led to the development of new assays. QuantiFERON-TB Gold (QFT-G) is an IFN-gamma-release assay that measures the release of interferon after stimulation in vitro by Mycobacterium tuberculosis antigens. The main advantage of this assay with respect to TST is the lack of crossreaction with bacillus Calmette-Guérin and most nontuberculous mycobacteria. QFT-G also eliminates the need for the patient to return for test reading in 48-72 h. In the immunocompromised host and in pediatric populations, studies suggest that the QFT-G better correlates with the risk of TB than the TST, but data remain inconclusive. In contrast to TST, there are no prospective studies regarding the association of the QFT-G result and the risk for development of TB. Given its advantages, the QFT-G may become the standard test for the diagnosis of LTBI.

Role of dendritic cells in the lung: in vitro models, animal models and human studies

Dendritic cells (DCs) are the most potent antigen-presenting cells in the human lung and are now recognized as crucial initiators of immune responses in general. They are arranged as sentinels in a dense surveillance network inside and below the epithelium of the airways and alveoli, where thet are ideally situated to sample inhaled antigen. DCs are known to play a pivotal role in maintaining the balance between tolerance and active immune response in the respiratory system. It is no surprise that the lungs became a main focus of DC-related investigations as this organ provides a large interface for interactions of inhaled antigens with the human body. During recent years there has been a constantly growing body of lung DC-related publications that draw their data from in vitro models, animal models and human studies. This review focuses on the biology and functions of different DC populations in the lung and highlights the advantages and drawbacks of different models with which to study the role of lung DCs. Furthermore, we present a number of up-to-date visualization techniques to characterize DC-related cell interactions in vitro and/or in vivo.

Oeuvres de La Bruyère (Nouvelle édition précédée d'un avant-propos)

Collection : Bibliothèque des chefs-d'oeuvre

Fastidious intracellular bacteria as causal agents of community-acquired pneumonia.

Intracellular bacteria are common causes of community-acquired pneumonia that grow poorly or not at all on standard culture media and do not respond to beta-lactam antibiotic therapy. Apart from well-established agents of pneumonia such as Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci and Coxiella burnetii, some new emerging pathogens have recently been recognized, mainly Parachlamydia acanthamoebae and Simkania negevensis, two Chlamydia-related bacteria. Most of them are causes of benign and self-limited infections. However, they may cause severe pneumonia in some cases (i.e., Legionnaires' disease) and they may cause outbreaks representing a public health problem deserving prompt recognition and appropriate therapy. Although extrapulmonary manifestations are often present, no clinical features allow them to be distinguished from classical bacterial agents of pneumonia such as Streptococcus pneumoniae. Thus, specific molecular diagnostic tools are very helpful for early recognition of the offending bacteria, whereas serology often only allows retrospective or late diagnosis. Macrolides remain the best empirical treatment of intracellular respiratory pathogens, although some observational studies suggest that quinolones may be superior for the treatment of legionellosis.

Resistance to Fusarium dry root rot disease in cassava accessions

The objective of this work was to identify sources of resistance to dry root rot induced by Fusarium sp. in cassava accessions. A macroconidial suspension (20 µL) of 11 Fusarium sp. isolates was inoculated in cassava roots, from 353 acessions plus seven commercial varieties. Ten days after inoculation, the total area colonized by the pathogen on the root pulp was evaluated by digital image analysis. Cluster analysis revealed the presence of five groups regarding resistance. The root lesion areas ranged from 18.28 to 1,096.07 mm² for the accessions BGM 1518 and BGM 556, respectively. The genotypes BGM 1042, BGM 1552, BGM 1586, BGM 1598, and BGM 1692 present the best agronomical traits.