Immune response to HIV.

PURPOSE OF REVIEW: Major advances have been made in the delineation of HIV-specific immune response and in the mechanisms of virus escape. The kinetics of the immunological and virological events occurring during primary HIV infection indicate that the establishment of the latent HIV reservoir, the major obstacle to HIV eradication likely occurs during the very early stages of primary infection, that is, the 'eclipse phase', prior to the development of the HIV-specific immune response which has limited efficacy in the control of the early events of infection. Therefore, the window of opportunity to develop effective interventions either to clear HIV during primary infection or to prevent rebound of HIV in patients successfully treated who stop antiretroviral therapy is very narrow. RECENT FINDINGS: Genetic factors most strongly associated with nonprogressive infection are human leukocyte antigen (HLA) class I alleles and particularly HLA-B5701. CD4 and CD8 T-cell responses with polyfunctional profile are associated with nonprogressive infection. Broader neutralizing antibodies are detected 3-4 years after infection, generated only in 20% of individuals but show no efficacy in the control of HIV replication. SUMMARY: In the present review, we shall discuss the different components of the HIV-specific immune response elicited by the infection, the kinetics of these responses during primary infection and the changes following transition to the chronic phase of infection, and the functional profile of 'effective' versus 'noneffective' HIV-specific immune responses.

Sport and alcohol: An emergency department study in Switzerland.

The aim of the present study was to empirically determine whether: (a) sport injuries were associated with alcohol consumption before the injury (acute intake) and with usual consumption patterns (chronic high intake and heavy intake on single occasions); (b) the risk of sport injuries related to alcohol consumption differs from that of other injuries; and (c) there are differences between the sexes and between types of sport. Data from 8694 patients attending the emergency department of Lausanne University Hospital between 1 January 2003 and 30 June 2004 were analysed. Of those patients, 4861 came to the hospital because of an injury and 885 patients were identified as having a sport injury (18.2%). Logistic regression was used to estimate the odds ratios of injury relating to alcohol consumption. With increasingly acute intake, the risk of sport and other injuries increased (sports injury and alcohol use in the 6 h before injury compared with no use: odds ratio=4.29, 7.46, and 14.75 for low, medium, and high alcohol use among women, and 2.81, 3.39, and 1.64 for low, medium, and high alcohol use among men). Alcohol consumption was associated with an increasingly higher risk of sport injuries compared with other injuries among women (consumption 6 h before injury: odds ratio=1.12, 1.23, and 1.56 for low, medium, and high alcohol use), but not men (odds ratio=1.17, 0.83, and 0.23 for low, medium, and high alcohol use). Regarding usual consumption patterns, those men and women injured while exercising were more often at-risk drinkers (men: 44%; women: 25%) compared with those injured during other activities (men: 37%; women: 13%). The results indicate that both men and women, but particularly women, should not practise sports after alcohol ingestion. The study raises questions as to whether sport should be generally promoted as an alternative to alcohol consumption in prevention programmes. Whereas some sports seem to be protective (e.g. endurance and fitness sport) for risky alcohol use, the majority are not. It is important to note, however, that we do not dismiss the beneficial effects of practising for an individual's health. The other positive aspect of practising, namely interacting socially with others, may come at the price of an increased alcohol use, particularly in a wet culture like Switzerland where any social contact is often accompanied by alcohol consumption.

La literatura jurídica, un mirall entelat de les guerres, les revoltes i les paus en la Catalunya dels anys 1640-1700

Aquest text s’emmarca en dos projectes de recerca: a) SEJ2006-15051-C03-01 “El derecho histórico en los pueblos de España: ámbitos público y privado (siglos XII-XXI)”, dirigit per Tomàs de Montagut, catedràtic d’Història del Dret a la UPF; b) HAR2008-03291/HIST “La formación del estado borbónico (1700-1746), dirigit per Joaquim Albareda, catedràtic d’Història Moderna també a la UPF.

Poxvirus vector-based HIV vaccines.

PURPOSE OF REVIEW: In this review, we will provide the scientific rationale for the use of poxvirus vectors in the field of HIV vaccines, the immunological profile of the vaccine-induced immune responses, an update on the current use of poxvirus vector-based vaccines in HIV vaccine clinical trials, and the development of new modified poxvirus vectors with improved immunological profile. RECENT FINDINGS: An Ad5-HIV vaccine was tested in a phase IIb clinical trial (known as the Step trial). Vaccinations in the Step trial were discontinued because the vaccine did not show any effect on acquisition of infection and on viral load. After the disappointing failure of the Step trial, the field of HIV vaccine has regained enthusiasm and vigour due to the promising protective effect observed in the phase III efficacy trial (known as RV-144) performed in Thailand which has tested a poxvirus-gp120 combination. SUMMARY: The RV-144 phase III has provided for the first time evidence that an HIV vaccine can prevent HIV infection. The results from the RV-144 trial are providing the scientific rationale for the future development of the HIV vaccine field and for designing future efficacy trials.

Online teaching of inflammatory skin pathology by a French-speaking International University Network

INTRODUCTION: Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. METHOD: One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. RESULTS: The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. CONCLUSION: The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging.

Developing psychosis and its risk States through the lens of schizotypy.

Starting from the early descriptions of Kraepelin and Bleuler, the construct of schizotypy was developed from observations of aberrations in nonpsychotic family members of schizophrenia patients. In contemporary diagnostic manuals, the positive symptoms of schizotypal personality disorder were included in the ultra high-risk (UHR) criteria 20 years ago, and nowadays are broadly employed in clinical early detection of psychosis. The schizotypy construct, now dissociated from strict familial risk, also informed research on the liability to develop any psychotic disorder, and in particular schizophrenia-spectrum disorders, even outside clinical settings. Against the historical background of schizotypy it is surprising that evidence from longitudinal studies linking schizotypy, UHR, and conversion to psychosis has only recently emerged; and it still remains unclear how schizotypy may be positioned in high-risk research. Following a comprehensive literature search, we review 18 prospective studies on 15 samples examining the evidence for a link between trait schizotypy and conversion to psychosis in 4 different types of samples: general population, clinical risk samples according to UHR and/or basic symptom criteria, genetic (familial) risk, and clinical samples at-risk for a nonpsychotic schizophrenia-spectrum diagnosis. These prospective studies underline the value of schizotypy in high-risk research, but also point to the lack of evidence needed to better define the position of the construct of schizotypy within a developmental psychopathology perspective of emerging psychosis and schizophrenia-spectrum disorders.

Physiological ligands of PPARs in inflammation and lipid homeostasis

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that are involved in many physiological processes, such as inflammation and energy homeostasis. In general, PPARs must be activated by ligands to stimulate the expression of their target genes. These agonists can be synthetic molecules, such as drugs used to treat hypertriglyceridemia and insulin resistance, or natural physiological ligands, such as fatty acids and eicosanoids. Although recent work has uncovered a surprisingly broad variety of natural molecules capable of activating PPARs, relatively little is known about their mode of action in an in vivo physiological context. The action of physiological ligands in situations of food deprivation and abundance, especially with respect to their intervention in the inflammatory response, and in both lipid homeostasis and inflammation resolution will be reviewed.

Le procès Pache : extraits du dossier ([Reprod.]) / avec introd. et notes par Adrien Sée,...

Collection : Les archives de la Révolution française ; 6.2.34