The "open" chimney graft technique for juxtarenal aortic aneurysms with discrepant renal arteries.

OBJECTIVES: A straightforward original Chimney Graft (CG) protocol has been developed at our institution in selected cases of juxtarenal aortic aneurysm (JRAA). The aim of this study was to present our clinical experience of consecutive series with use of uncovered self-expanding stent (SES) as "Open Chimney" (OCh) in the endovascular repair (EVAR) of JRAA. METHODS: A standard endograft with suprarenal fixation struts is delivered with its proximal covered edge just below the highest RA in JRAA presenting the ostium of the two renal arteries at a different aortic level and the distance between the highest renal artery and the beginning of the aneurysm (improved landing zone) ≥10 mm. The low-lying renal artery is maintained patent by the OCh graft (standard SES) delivered from left brachial access (6 Fr). All clinical, anatomical, and operative data were prospectively collected and retrieved for the study analysis. RESULTS: From July 2010 to November 2012, OCh EVAR was offered to 22 consecutive patients considered unfit for JRAA open repair. All procedures were technically successful with aneurysm exclusion and patent OCh graft. One small perioperative type Ia endoleak spontaneously disappeared at the 3-month CT control. One patient died because of acute decompensated heart failure. One patient presented a left hemispheric stroke. The median follow-up of 18 months (range 7-35) showed aneurysm exclusion in all patients without type I and III endoleaks, SES stenosis, and/or renal impairment. CONCLUSIONS: OCh-EVAR is a straightforward technique that can be employed in selected cases of JRAA, avoiding the more complex and expensive fenestrated EVAR.

Accidentologic aspects of helicopter rescue missions involving winching of a physician

Introduction: Medical helicopter services provide several advantages,like the ability to perform air searches for lost victims, a rapid method ofshuttling rescue personnel and equipment to the victim, and the deliveryof early on-site advance medical care. When landing is not possible, therescuers can also be directly winched to the victim. As outdoor activitiesare increasing, few data are available about the type of accidentsleading to a rescue operation involving the use of the winch. We soughtto study the epidemiology and accidentology of such rescues.Methods: We retrospectively reviewed the medical reports of a singlehelicopter-based emergency medical service. Data from 1 January 2003to 31 December 2008 were analyzed. Cases with emergency callindicating that the victim was deceased were excluded. Data includedthe age and gender of the patients, the type of patients activitypreceeding the injury, the mecanism of injury, and the type of lesions(main diagnosis).Results: 9879 rescue missions were conducted between 1 January2003 and 31 December 2008. The 921 (9.3%) missions involvingwinching of the emergency physician were analysed. The male:femaleratio of the patients was 2:1. There were 56 (6%) patients aged 15 orunder. Most of the patients, while injured, were practising winter sportsor mountain-related activities in the summer (table 1). Falls accountedfor the great majority of the trauma events (700 patients or 76%),followed by illnesses (81 patients or 9 %). Of the 921 missions in whichthe physician was winched in the field, 28 (3%) were avalanche rescuesand 13 (1%) were glacier crevasse rescues. Trauma to the upper andlower extremities accounted for 429 (47%) of all injuries, followed by175 (19%) head injuries and 108 (12%) spinal lesions. Hypothermia,frostbite and altitude illnesses were diagnosed in 11 (1%) cases.In 128(14%) cases two different diagnoses were made, and in 69 (7%) threeor more diagnoses.Conclusions: In our helicopter emergency base, between 2003 and2008, 921 rescue missions (9.3%) involved winching of the emergencydoctor. Patients rescued using the winch usually practice outdoorsports, and are predominantly male. The mechanism of the injury isusually a fall, and extremities and head injuries account for more than50% of the main diagnosis made on the field.

Biochemical characterization of FANCD2 and FANCM in the Fanconi Anaemia pathway

Abstract : The maintenance of genome stability is a challenge for all living organisms. DNA is regularly subjected to chemical alterations by both endogenous and exogenous DNA damaging agents. If left unrepaired, these lesions will create mutations or lead to chromosomal instability. DNA crosslinking agents probably bring about the most toxic lesions. By linking covalently the two strands of DNA, crosslinking agents will impede essential cellular processes such as replication and transcription. Cells from Fanconi anaemia patients are extremely sensitive to these agents. Fanconi anaemia (FA) is a rare chromosomal instability disorder that leads to developmental defects, pancytopenia and cancer susceptibility. FA is a genetically heterogeneous disease with thirteen complementation groups identified. Proteins encoded by the FA genes work together in the FA pathway. Eight of these proteins form the FA core complex (FANC-A, B, C,E, F, G, L and -M), whose integrity is required to monoubiquitinate FANCD2 and FANCI in response to DNA damage. The hypersensitivity of FA cells to crosslinking agents, which perturb the progression of replication forks, has led to the hypothesis that FA proteins play a crucial role in the response to replication stress. However, at the molecular level, the functions of the FA pathway remain largely unknown. Our efforts were first focused on the characterization of FANCD2, "the key effector of the FA pathway". Using different substrates, we found that in vitro, purified hFANCD2 preferentially binds single strand DNA and double strand DNA extremities. Concomitantly, FANCM was identified as a new component of the FA core complex. Moreover FANCM was shown to have specific branch migration activities and probably a role as a "landing platform" on DNA for the other components of the core complex. By using FANCM mutants carrying deletions within the internal domain, we investigated the role of FANCM as a DNA anchor protein for the core complex. We observed that indeed, a specific part of the internal domain of FANCM interacts with components of the core complex. Finally, in collaboration with Weidong Wang's lab we characterized two new components of the FA pathway: FAAP10 and FAAP16. As a heterodimer these two proteins show affinity for dsDNA, and anneal complementary oligonucleotides in vitro. Moreover these proteins can associate with FANCM via a part of its internal domain. We find that FANCM, FAAP 10 and FAAP 16 can co-exist on the branch point of replication and recombination intermediates, and that FAAP10 and FAAP16 stimulate replication fork reversal by FANCM. These results suggest that FANCM may function as a landing platform for the core complex. After loading on DNA, the core complex can activate FANCD2 through monoubiquitination leading to its recruitment to the site of damage. Since ssDNA and double strand breaks are intermediates that are generated as a consequence of collapsed replication forks, FANCD2 by binding to ds DNA ends and ssDNA could protect such structures from the recombination repair machinery and prevent unscheduled recombination events. Alternatively, FANCD2 could avoid nucleases from gaining access to collapsed forks, preserving the DNA in state that can be used as a starting point for resumption of DNA synthesis. The overall comprehension of the FA pathway is far from been complete. Our results unravel new aspects of Fanconi Anaemia, which hopefully in the near future will address keys questions leading to a better understanding of the fascinating Fanconi Anaemia. Résumé : Le maintien de l'intégrité du génome est fondamentale chez tous les organismes vivants. L'ADN est constamment altéré par des composés aussi bien endogènes qu'exogènes. Si ces altérations ne sont pas réparées, elles peuvent conduire à l'apparition de mutations, ainsi qu'à une instabilité génomique accrue. Les lésions les plus sévères qui peuvent survenir sur l'ADN, sont les pontages inter caténaires. Des agents pontants en liant de façon covalente les deux brins d'ADN, vont empêcher le déroulement normal de processus cellulaires essentiels tels que la réplication ou la transcription. La compréhension des mécanismes permettant à la cellule de tolérer et réparer ces lésions est primordiale, notamment dans le cas des patients atteints de l'anémie de Fanconi qui présentent une très grande sensibilité à ces composés pontants. L'anémie de Fanconi est une maladie génétique rare appartenant à un groupe de pathologies associées à une grande instabilité chromosomique. Les patients atteints de l'anémie de Fanconi présentent des malformations du squelette, une pancytopénie et une forte propension à la survenue de cancer. L'anémie de Fanconi est génétiquement très hétérogène. À ce jour, 13 gènes codant pour 13 protéines FANC différentes ont été identifiés. Huit de ces protéines fonctionnent ensemble au sein d'un complexe (nommé le complexe FANC) ayant pour but de monoubiquitiner FANCD2 et FANCI en réponse à la formation de lésions sur l'ADN. L'extrême sensibilité des cellules de patients atteints de l'anémie de Fanconi à ces agents pontant l'ADN suggère l'implication des protéines FANC dans la réponse cellulaire suite à une stress réplicatif. Cependant, le rôle moléculaire exact de ces protéines demeure encore inconnu. Après purification, nous avons observé que FANCD2 était capable de lier l'ADN simple brin, ainsi que les extrémités d'ADN in vitro. Dans le même temps, FANCM fut identifié comme appartenant au complexe FANC. FANCM est décrit comme une translocase capable de promouvoir le déplacement de point de jonction dans des structures d'ADN spécifiques in vitro. De plus, en se liant à l'ADN, FANCM peut agir comme une plateforme pour les autres protéines FANC, leur permettant ainsi d'être adressées à l'ADN. En créant des protéines FANCM recombinantes ayant des délétions dans le domaine interne, nous avons pu observer que certaines protéines du complexe FANC se fixent à des sites spécifiques sur le domaine interne de FANCM. Enfin, au travers d'une collaboration, nous avons été amenés à caractériser deux nouvelles protéines appartenant au complexe FANC : FAAP 10 et FAAP16. Elles s'associent à FANCM par l'intermédiaire du domaine interne, et forment ainsi un hétérotrimére. La présence de FAAP10 et FAAP16 n'affecte pas la liaison de FANCM à l'ADN, mais semble potentialiser son activité de régression in vitro. FANCM semble donc fonctionner comme une plateforme pour les autres composants du complexe FANC. Ces derniers, une fois liés à l'ADN permettent la monoubiquitination de FANCD2 et son recrutement au site lésé de l'ADN. FANCD2 en se liant de façon préférentielle à l'ADN simple brin et aux extrémités d'ADN qui sont générés lors de l'arrêt et du démantèlement d'une fourche de réplication, pourrait protéger ces même fourches de réplication arrêtées, d'évènements de recombinaison aléatoires. Nos résultats apportent de nouveaux éléments concernant les mécanismes moléculaires de l'anémie de Fanconi. Enfin, l'étude de l'anémie de Fanconi permet aussi de mieux comprendre les mécanismes mis en place par la cellule pour tolérer des lésions survenant lors de la réplication.

A spatial modelling framework for assessing climate change impacts on freshwater ecosystems: Response of brown trout (Salmo trutta L.) biomass to warming water temperature

Mountain regions worldwide are particularly sensitive to on-going climate change. Specifically in the Alps in Switzerland, the temperature has increased twice as fast than in the rest of the Northern hemisphere. Water temperature closely follows the annual air temperature cycle, severely impacting streams and freshwater ecosystems. In the last 20 years, brown trout (Salmo trutta L) catch has declined by approximately 40-50% in many rivers in Switzerland. Increasing water temperature has been suggested as one of the most likely cause of this decline. Temperature has a direct effect on trout population dynamics through developmental and disease control but can also indirectly impact dynamics via food-web interactions such as resource availability. We developed a spatially explicit modelling framework that allows spatial and temporal projections of trout biomass using the Aare river catchment as a model system, in order to assess the spatial and seasonal patterns of trout biomass variation. Given that biomass has a seasonal variation depending on trout life history stage, we developed seasonal biomass variation models for three periods of the year (Autumn-Winter, Spring and Summer). Because stream water temperature is a critical parameter for brown trout development, we first calibrated a model to predict water temperature as a function of air temperature to be able to further apply climate change scenarios. We then built a model of trout biomass variation by linking water temperature to trout biomass measurements collected by electro-fishing in 21 stations from 2009 to 2011. The different modelling components of our framework had overall a good predictive ability and we could show a seasonal effect of water temperature affecting trout biomass variation. Our statistical framework uses a minimum set of input variables that make it easily transferable to other study areas or fish species but could be improved by including effects of the biotic environment and the evolution of demographical parameters over time. However, our framework still remains informative to spatially highlight where potential changes of water temperature could affect trout biomass. (C) 2015 Elsevier B.V. All rights reserved.-