Mechanisms of lipid malabsorption in Cystic Fibrosis: the impact of essential fatty acids deficiency

Affiliation: CHU-Sainte-Justine, Université de MontréalTransport mechanisms, whereby alimentary lipids are digested and packaged into small emulsion particles that enter intestinal cells to be translocated to the plasma in the form of chylomicrons, are impaired in cystic fibrosis. The purpose of this paper is to focus on defects that are related to intraluminal and intracellular events in this life-limiting genetic disorder. Specific evidence is presented to highlight the relationship between fat malabsorption and essential fatty acid deficiency commonly found in patients with cystic fibrosis that are often related to the genotype. Given the interdependency of pulmonary disease, pancreatic insufficiency and nutritional status, greater attention should be paid to the optimal correction of fat malabsorption and essential fatty acid deficiency in order to improve the quality of life and extend the life span of patients with cystic fibrosis

Genital Schistosomiasis in European Women

Female genital schistosomiasis (FGS) is an isolated chronic form of schistosomiasis. Although most infections occur in residents of endemic areas, it has been clearly documented that brief freshwater exposure is sufficient to establish infection; thus, travellers may also be infected. The clinical manifestations of FGS are nonspecific, and lesions may mimic any neoplastic or infectious process in the female genital tract. It is important to take a careful history and physical examination, making sure to consider travel history in endemic areas. The diagnosis is confirmed by microscopy with egg identification or by serology. The standard of care for treatment is a single dose of oral praziquantel which avoids complications and substantial morbidity. Herein, we report a rare and original case of FGS in a European woman

Reliability of molecular host-identification methods for ticks: an experimental in vitro study with Ixodes ricinus

Background: Reliable information on host use by arthropod vectors is required to study pathogen transmission ecology and to predict disease risk. Direct observation of host use is often difficult or impossible and indirect methods are therefore necessary. However, the reliability of currently available methods to identify the last host of blood-feeding arthropods has not been evaluated, and may be particularly problematic for ticks because host blood has been digested at capture. Biases in host detection may lead to erroneous conclusions on both vector ecology and pathogen circulation. Methods: Here, we experimentally tested for biases in host detection using the generalist three-host tick Ixodes ricinus as a model system. We fed ticks using an artificial feeding system and amplified blood meal traces post-moult (i.e., in the succeeding unfed life stage) via both a quantitative real-time polymerase chain reaction assay and a reverse line blotting method. We then experimentally tested for three types of biases in host detection: 1) time post-moult, 2) tick life stage and 3) host type (non-nucleated mammal blood versus nucleated avian blood), and compared these biases between the two molecular methods. Results: Our results show that all three factors can influence host detection in ticks but not necessarily in the expected way. Although host detection rates decreased with time post-moult, mammal blood tended to be more readily detected than bird blood. Tick life stage was also an important factor; detection was higher in nymphs than in adults and, in some cases, remnants from both larval and nymphal blood meals could be detected in the adult stage. These biases were similar for the two detection techniques. Conclusions: We show that different factors associated with questing ticks may influence our ability to correctly infer previous host use and that these factors may bias inferences from field-based studies. As these biases may be common to other vector-borne disease systems, their implications for our understanding of vector ecology and disease transmission require more explicit consideration

Optical spectroscopy for real-time neuronavigation during deep brain stimulation surgeries

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Elimination of HIV-1-infected cells by broadly neutralizing antibodies.

International audienceThe Fc region of HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) is required for suppressing viraemia, through mechanisms which remain poorly understood. Here, we identify bNAbs that exert antibody-dependent cellular cytotoxicity (ADCC) in cell culture and kill HIV-1-infected lymphocytes through natural killer (NK) engagement. These antibodies target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The landscape of Env epitope exposure at the surface and the sensitivity of infected cells to ADCC vary considerably between viral strains. Efficient ADCC requires sustained cell surface binding of bNAbs to Env, and combining bNAbs allows a potent killing activity. Furthermore, reactivated infected cells from HIV-positive individuals expose heterogeneous Env epitope patterns, with levels that are often but not always sufficient to trigger killing by bNAbs. Our study delineates the parameters controlling ADCC activity of bNAbs, and supports the use of the most potent antibodies to clear the viral reservoir

Sanar nuestros vínculos para sanar el vínculo: del león al unicornio, pasando por el mono

En los últimos años, el término “incasable”, para quien no hay lugar, se utiliza cada vez más para describir a niñas, niños y jóvenes que agotan las instituciones y son zarandeados de una a otra. A partir de la presentación de la trayectoria vital y la hospitalización de una niña de 10 años con apego inseguro, desorganizado y síntomas de disociación postraumática, en el artículo se exploran los elementos que sustentaron su atención. Entre ellos, se hace especial hincapié en la importancia de los vínculos difractores y las relaciones transferenciales, tanto dentro de la unidad de atención como dentro de la institución; también se observan las vinculaciones entre estas y quienes conforman la red de la niña. Se proponen la función y el uso de determinados objetos y un modelo de coterapia por parte de un psicólogo y un fisioterapeuta. Por último, se presenta el testimonio de la niña recogido en forma de juego de arena y las reflexiones que de él se desprenden

Catalytically inactive human cathepsin D triggers fibroblast invasive growth

The aspartyl-protease cathepsin D (cath-D) is overexpressed and hypersecreted by epithelial breast cancer cells and stimulates their proliferation. As tumor epithelial–fibroblast cell interactions are important events in cancer progression, we investigated whether cath-D overexpression affects also fibroblast behavior. We demonstrate a requirement of cath-D for fibroblast invasive growth using a three-dimensional (3D) coculture assay with cancer cells secreting or not pro-cath-D. Ectopic expression of cath-D in cath-D–deficient fibroblasts stimulates 3D outgrowth that is associated with a significant increase in fibroblast proliferation, survival, motility, and invasive capacity, accompanied by activation of the ras–MAPK pathway. Interestingly, all these stimulatory effects on fibroblasts are independent of cath-D proteolytic activity. Finally, we show that pro-cath-D secreted by cancer cells is captured by fibroblasts and partially mimics effects of transfected cath-D. We conclude that cath-D is crucial for fibroblast invasive outgrowth and could act as a key paracrine communicator between cancer and stromal cells, independently of its catalytic activity

Clinicians' adherence versus non adherence to practice guidelines in the management of patients with sarcoma: a cost-effectiveness assessment in two European regions

International audienceABSTRACT: BACKGROUND: Although the management of sarcoma is improving, non adherence to clinical practice guidelines (CPGs) remains high, mainly because of the low incidence of the disease and the variety of histological subtypes. Since little is known about the health economics of sarcoma, we undertook a cost-effectiveness analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing costs and outcomes when clinicians adhered to CPGs and when they did not. METHODS: Patients studied had a histological diagnosis of sarcoma, were older than 15 years, and had been treated in the Rhone-Alpes region of France (in 2005/2006) or in the Veneto region of Italy (in 2007). Data collected retrospectively for the three years after diagnosis were used to determine relapse free survival and health costs (adopting the hospital's perspective and a microcosting approach). All costs were expressed in euros at their 2009 value. A 4% annual discount rate was applied to both costs and effects. The incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse-free year gained when management was compliant with CPGs compared with when it was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity analysis was performed based on a non-parametric bootstrap method. RESULTS: A total of 219 patients were included in the study. Compliance with CPGs was observed for 118 patients (54%). Average total costs reached 23,571 euros when treatment was in accordance with CPGs and 27,313 euros when it was not. In relation to relapse-free survival, compliance with CPGs strictly dominates non compliance, i.e. it is both less costly and more effective. Taking uncertainty into account, the probability that compliance with CPGs still strictly dominates was 75%. CONCLUSIONS: Our findings should encourage physicians to increase their compliance with CPGs and healthcare administrators to invest in the implementation of CPGs in the management of sarcoma

Genomic changes during the evolution of the Coxiella genus along the parasitism-mutualism continuum

The Coxiellaceae family is composed of five genera showing lifestyles ranging from free-living to symbiosis. Among them, Coxiella burnetii is a well-known pathogen causing Q fever in humans. This bacterium presents both intracellular (parasitic) and environmental (resistant) forms. Recently, several environmental Coxiella genomes have been reported, among which several have come from intracellular mutualistic symbionts of ticks, termed Coxiella-like endosymbionts. We sequenced two new Coxiella-LE genomes from Dermacentor marginatus (CLEDm) and Ornithodoros maritimus (CLEOmar) ticks, the latter belonging to the C. burnetii lineage. Using these newly sequenced Coxiella-LEs and 43 Coxiellaceae genomes, we conducted comparative genomic and phylogenomic analyses to increase our knowledge of C. burnetii pathogenicity and the emergence of Coxiella-LEs. Results highlight the probably parasitic nature of the common ancestor of the Coxiellaceae. Indeed, the virulence factor Dot/Icm T4 Secretion System is present in most, but not all, Coxiellaceae. Whereas it is part of a putative pathogenic island in C. burnetii, it has been entirely lost or inactivated in Coxiella-LEs, suggesting its importance in pathogenesis. Additionally, we found that a Sha/Mrp antiporter was laterally acquired in the C. burnetii lineage. This antiporter might be involved in alkali resistance and the development of the resistant form that is able to persist in the environment for long periods of time. The Sha operon is eroded or absent in Coxiella-LEs. Finally, we found that all Coxiella representatives produce B vitamins and co-factors indicating a pre-adaptation of Coxiella to mutualism with hematophagous arthropods. Accordingly, the ancestor of C. burnetii and Coxiella-LEs was likely a parasitic bacterium able to manipulate its host cell and to produce vitamins and co-factors for its own use